Markers For Endometrial Cancer

Abstract

The invention relates to the surprising finding that biomarkers corresponding to ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN are differentially expressed in control samples as compared to samples from patients having endometrial cancer and are therefore useful for detecting endometrial cancer. In particular these biomarkers having excellent sensitivity, specificity, and/or the ability to separate affected from non affected individuals. Furthermore, the inventors found that the differential expression of these biomarkers in primary endometrial cancer tumor tissue is correlated to their expression level in uterine fluid samples as compared to control values. Thus these biomarkers are robust in that they are found to be differentially expressed in several different types of samples from affected and individuals.

Description

CROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application is a Divisional of U.S. patent application Ser. No. 13/386,536, filed Jan. 23, 2012, which was filed as the National Phase of International Patent Application No. PCT/EP2010/004550, filed Jul. 23, 2010, which claims priority to Europe Patent Application No. 09166398.9, filed Jul. 24, 2009. The contents of these applications are herein incorporated by reference in their entirety.

FIELD OF THE INVENTION

[0002] The invention relates to the detection diagnosis, and prognosis of uterine cancer. The invention relates to the surprising finding that biomarkers corresponding to ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN are differentially expressed in control samples as compared to samples from patients having endometrial cancer and are therefore useful for detecting endometrial cancer. In particular these biomarkers having excellent sensitivity, specificity, and/or the ability to separate affected from non affected individuals. Furthermore, the inventors found that the differential expression of these biomarkers in primary endometrial cancer tumor tissue is correlated to their expression level in uterine fluid samples as compared to control values. Thus these biomarkers are robust in that they are found to be differentially expressed in several different types of samples from affected and individuals.

BACKGROUND OF THE INVENTION

[0003] Each year in Europe there are about 150,000 new cases of endometrial cancer and about 46,000 women die from the disease (Ferlay et al. (2007) Ann. Onc. 18:581-592). In the United States, about 41,000 new case of endometrial carcinoma are diagnosed per year and 7,300 women die each year (see American Cancer Society statistics available on the internet). The incidence and death rate from endometrial cancer are increasing.

[0004] Endometrial cancer (EC) is the most frequent invasive tumors of the female genital tract and the fourth most common in women in western countries (Jemal et al. (2008) CA Cancer J Clin 58:71-96). New methods for the diagnosis, prognosis, and classification of endometrial cancer are needed to combat this deadly disease.

[0005] Often endometrial cancer is detected early, in its initial stages, by presentation of disease-related symptoms. Unfortunately, 20% of patients present with myometrial invasion and/or lymph node affectation, which are main indicators related to poor prognosis, decrease in survival rate, and more advanced disease. The primary therapeutic modality for endometrial cancer is surgical treatment.

[0006] Common symptoms of uterine cancer (e.g., endometrial cancer) include unusual vaginal bleeding or discharge, trouble urinating, pelvic pain, and pain during intercourse. Uterine cancer usually occurs after menopause. Other risk factors for endometrial cancer include being obese, taking estrogen-alone hormone replacement therapy, treatment with tamixofen and having a genetic predisposition to cancer (e.g., Lynch Syndrome). The standard treatment for endometrial cancer varies depending on the stage of the disease. Treatment usually involves surgery to remove the uterus which is called a hysterectomy, although other options include hormone therapy and radiotherapy.

[0007] Methods routinely used in the clinic for diagnosing endometrial cancer include biopsy followed by cytological analysis and/or trans-vaginal ultrasound. The diagnosis of endometrial carcinoma is usually done by pathology examination of an endometrial aspirate (20-30%), and by biopsy-guided hysteroscopy (70-80%). The rate of success of diagnosis with hysteroscopy is over 90%, with false positives in the case of precursor lesions of the endometrial adenocarcinoma (hyperplasias); endometrial polyps, that present a non-negligible degree of malignancy (0-4.8%) and must be removed although asymptomatic or benign appearance; or in the case of diffuse forms of endometrial adenocarcinomas that are difficult to differentiate from an endometrial hyperplasia. Thus, there is a need for a less invasive diagnostic test based on molecular markers. Such a less invasive test based on molecular markers would allow for more routine screening of uterine cancer. A diagnostic test based of molecular markers obtained in a less invasive manner and that has sensitivity and specificity comparable to that of the endometrial biopsy can preclude unnecessary hysteroscopy.

[0008] Endometrial carcinomas can be classified into low grade (type I) and high-grade (type 2). Type I endometrioid endometrial cancer (sometimes called estrogen dependent), which represent approximately 80% of new cases, are low grade tumors associated with estrogen stimulation, usually developed in peri- or post-menopausal women and are usually preceded by endometrial hyperplasia with or without atypia. Type II non-endometrioid endometrial cancer usually affects older women, are less differentiated and of worse prognosis, not associated with estrogen stimulation, and are related to atrophic endometrium or, occasionally, with endometrial polyps.

[0009] Type I cancers are typically known to have alterations in PTEN, KRAS2, DNA mismatch repair defects, CTNNB1, and have near diploid karyotype. Type II cancers typically have TP53 mutations and ErBB2 overexpression and are mostly non-diploid. Sugiyama et al. ((2003) Clin. Can. Res. 9:5589-5600) reported that certain genes are selectively up or down regulated in type I versus type II endometrial cancers. For example, they found that MLH1 was down-regulated in type I cancers as well as other genes related to DNA damage signaling and repair like O.sup.6-methyl-guanine DNA methyltransferase, DNA polymerase a catalytic subunit, and Ku (p70/p80) antigen. VEGF-C was found to be upregulated in type I cancers at the protein and mRNA level as compared to type II cancers. KRAS was found to be upregulated in type II cancers. STAT1 was upregulated in type I cancers and STAT2 was upregulated in type II cancers. Konecny et al. ((2009) British Journal of Cancer 100, 89-95) report that the rate HER2 gene amplification as measured by fluorescence in situ hybridization was greater in type II cancers whereas EGFR expression as measured by IHC techniques was significantly lower in type II cancers. Deng et al. ((2005) Clin. Can. Res. vol. 11, no 23:8258-8264) report that EIG121 is a marker for type I estrogen associated cancers.

[0010] Uterine cancers are also classified histologically according to cell-type. The most common cell-type is referred to endometrioid and represents around 80% of the newly diagnosed cases. Other less common uterine cancers are referred to as serous and clear cell carcinomas. Most of the type I cancers are of the endometrioid cell-type whereas the type II cancers are more likely to be non-endometrioid uterine cancers. Type II cancers are more likely to metastasize and have a poorer prognosis than type I cancers. Type I cancers typically have a better prognosis and respond better to therapy.

[0011] A number of studies have examined gene-expression profiles for classifying uterine cancers. Sugiyama et al. ((2003) Clin. Canc. Res. 9:5589-5600) report that between the type I and II cancers 45 gene were highly expressed in type I cancers and 24 highly expressed in type I cancers. Risinger et al. ((2003) Canc. Res. 63:6-11) report that microarray analysis of different histologic subtypes of endometrial cancer have distinct gene expression profiles. They found that 191 genes exhibited greater than 2-fold difference in expression between endometrioid and non-endometrioid endometrial cancers.

[0012] A number of endometrial cancer biomarkers for endometrial cancer have been identified. Elevated levels of CA 125, CA 15-3, and CA 19-9 are associated with shorter survival time. CA 125 correlates with tumor size and stage and is an independent predictor of the extrauterine spread.

[0013] Serum markers for the detection of uterine cancer have been reported in the literature. Yurkovetsky et al. ((2007) Gyn. Onc. 107:58-65) identified that prolactin is a serum biomarker with sensitivity and specificity for endometrial cancer. They found serum CA 125, CA 15-3, and CEA, are higher in patients with Stage III disease as compared to stage I. A five-biomarker panel of prolactin, GH, eotaxin, E-selectin, and TSH discriminated endometrial cancer from ovarian and breast cancer.

[0014] Another important issue for clinicians for diagnosis of endometrial cancer relates to synchronous cancers. Guirguis et al. (Gyn. Onc. (2008) 108:370-376) have reported that 10% of ovarian cancer patients have a tumor in the endometrium and 5-25% of patients with endometrial cancer also have a tumor in the ovary. Determining the primary site of a cancer has important treatment implications. Stage III endometrial carcinoma is treated with surgery followed by chemotherapy and/or radiation; while dual primary stage I ovarian and endometrial cancers have a better prognosis and may not require adjuvant therapy.

[0015] Current methods of diagnosing endometrial cancer often create discomfort to the patient and sometimes rely on subjective interpretation of visual images. There is a need for less invasive methods of screening for endometrial cancer which are less subjective in interpretation. In addition there is a need for new markers that are useful for the early detection of endometrial cancer. Current methods for detecting endometrial cancer include the dilation and curettage method which is considered the gold standard, but this method is invasive, can cause significant discomfort, and may require a trained pathologist for interpretation, and therefore is not suitable as a general screening tool. Another less invasive method for diagnosing endometrial cancer involves transvaginal ultrasound which measures the thickness of the endometrium. In a study of patients having post-menopausal bleeding, using a cutoff of 4 mm, it was found that transvaginal ultrasound had 100% sensitivity and 60% specificity (Gull et al. (2003) Am. J. Obstet. Gynecol. 188(2):401-408). In women without vaginal bleeding, the sensitivity of the endometrial thickness measurement was 17% for a threshold 6 mm and 33% for a threshold of 5 mm (Fleischer et al. (2001) Am. J. Obstet. Gynecol. 184:70-75). TVS has a high rate of false positives since other conditions besides endometrial cancer can produce a thicker endometrium. One potential problem with the use of TVS in pre- and peri-menopausal women is that the thickness of the endometrium varies as a function of the phase of the menstrual cycle. Furthermore, women taking tamoxifen also have thicker endometrium. Therefore there is a need for techniques and markers that can complement and/or improve the ability of TVS in the diagnosis of endometrial cancer.

[0016] Clearly there is room for improvement in the tools currently available for screening for endometrial cancer.

BRIEF SUMMARY OF THE INVENTION

[0017] The invention relates to the surprising finding that biomarkers corresponding to ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN are differentially expressed in control samples as compared to samples from patients having endometrial cancer and are therefore useful for detecting endometrial cancer. In particular these biomarkers having excellent sensitivity, specificity, and/or the ability to separate affected from non affected individuals. Furthermore, the inventors found that the differential expression of these biomarkers in primary endometrial cancer tumor tissue is correlated to their expression level in uterine fluid samples as compared to control values. Thus, these biomarkers are robust in that they are found to be differentially expressed in several different types of samples from affected individuals as compared to non-affected individuals. Therefore, the present invention relates to an in vitro diagnostic method for the diagnosis of endometrial cancer or an increased likelihood of endometrial comprising detecting the level of

(1) from 1 to 17 biomarker(s) chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, and TJP3 in a sample from a patient wherein an increased level of said from 1 to 17 biomarkers compared to a control value indicates a diagnosis of endometrial cancer or increased likelihood of endometrial cancer and/or (2) detecting the level of from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN, wherein a decreased level of EFEMP2, SOCS2, and/or DCN compared to a control value indicates a diagnosis of endometrial cancer or increased likelihood of endometrial cancer.

[0018] Accordingly, the present invention relates to an in vitro diagnostic method for the diagnosis of endometrial cancer comprising

(1) detecting the level of from 1 to 17 biomarker(s) chosen from P4HB, GMIP, IKBKE, FASTKD1, DDR1, SIRT6, PHKG2, ACAA1, AP1M2, EPS8L2, P2RX4, PPFIBP2, PPP1R16A, CGN, RASSF7, RNF183, and TJP3 in a sample from a patient wherein an increased level of said from 1 to 17 biomarkers compared to a control value indicates the existence of endometrial cancer and/or (2) detecting the level of from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN, wherein a decreased level of EFEMP2, SOCS2, and/or DCN compared to a control value indicates the existence of endometrial cancer.

[0019] The biomarkers of Table 1 were found to be differential expressed between endometrial cancer samples and normal samples as determined by microarray studies (see Table 1 in the Detailed Description of the Invention). The inventors have found that individually each of the biomarkers of Table 1 have predictive value for the diagnosis of endometrial cancer. Furthermore, the levels of combinations of markers of Table 1 have additional predictive value for the diagnosis of endometrial cancer (See Example 5). For example, the inventors have surprisingly found that sub-groups of the biomarkers of Table 1 having from 2-20 biomarkers in various combinations to give fingerprint patterns have excellent predictive value for diagnosis or detection of endometrial cancer. Generally, if more than one of the biomarkers of Table 1 are differentially expressed in a sample, this increases the likelihood that the individual has endometrial cancer. Moreover, the inventors have also found that addition of other biomarkers besides those listed in Table 1, to the fingerprint pattern also can increase predictive value, and can be useful for classifying endometrial cancers, for differential diagnosis of diseases other than endometrial cancer, and for endometrial cancer prognosis. Table 1 lists the ENSEMBL accession numbers for the genes, mRNA, and proteins corresponding to the biomarkers of the invention. Some of the biomarkers have alternative transcripts. The invention relates to determining the differential expression of any of these alternative transcripts (or protein isoforms) as long as it expression is correlated with the absence or presence of endometrial cancer. Preferred transcripts (or protein isoforms) for detecting endometrial cancer are those which were detected with the array probes as indicated in the Examples.

[0020] The inventors have also found that the markers of Table 1 can be detected in uterine fluid samples and that the level of expression of these markers are correlated in primary tumor and uterine fluid (e.g., obtained by a uterine wash or aspiration).

[0021] The invention therefore provides methods for determining the level of from 1 to 20 of the biomarkers listed in Table 1 in a test sample. The method can comprise providing or obtaining a test sample from the patient; determining the level of from 1 to 20 of the biomarkers of Table 1 in the sample; and comparing the level of the biomarker(s) in the test sample(s) to a control value (e.g., control sample, control value, or control score). A higher level of biomarker(s) which was found to be overexpressed in endometrial cancer as shown in Table 1 in the test sample obtained from the patient compared to the control value (e.g., control sample, control value, and/or control score) indicates endometrial cancer, an increased likelihood of endometrial cancer, and/or a precancerous condition (e.g., endometrial hyperplasia). A lower level of biomarker(s) which was found to be underexpressed in endometrial cancer as shown in Table 1 in the test sample obtained from the patient compared to level in the control value (e.g., control sample, control value, and/or control score) indicates endometrial cancer, an increased likelihood of endometrial cancer, and/or a precancerous condition (e.g., endometrial hyperlasia). The level of the biomarker(s) can be determined using appropriate assays, including RT-PCR, quantitative PCR, multiplex PCR, Northern hybridization, microarray analysis, two-hybrid assays such as GAL4 DNA binding domain based assays, antibody based assays, EIA, blot assays, sandwich assays, and the like. The level of the biomarkers of Table 1 can be determined in body fluids and tissues for the diagnosis of endometrial cancer. The level of the biomarkers of Table 1 can be determined in tumor tissue obtained by biopsy for example. The level of the biomarkers of Table 1 can be determined in samples obtained from uterine aspirates and/or fluid. The level of the biomarkers of Table 1 can be determined in blood, serum, or plasma.

[0022] The biomarkers of Table 1 include ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, and TJP3, which were found to be upregulated in endometrial cancer and DCN, SOCS2, and EFEMP2 which were found to be down regulated in endometrial cancer in these studies. In one embodiment, the biomarkers for use in the method of the invention for detecting endometrial cancer or an increased likelihood of endometrial cancer include from 1 to 17 of the upregulated biomarkers listed in Table 1 and from 1 to 3 of the downregulated markers listed in Table 1.

[0023] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising obtaining a sample from an individual and determining the level of one or more biomarkers chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0024] Accordingly, the present invention relates to an in vitro diagnostic method for the diagnosis of endometrial cancer comprising

(1) detecting the level of one or more biomarker(s) chosen from P4HB, GMIP, IKBKE, FASTKD1, DDR1, SIRT6, PHKG2, ACAA1, AP1M2, EPS8L2, P2RX4, PPFIBP2, PPP1R16A, CGN, RASSF7, RNF183, and TJP3 in a sample from a patient wherein an increased level of said one or more biomarkers compared to a control value indicates the existence of endometrial cancer and/or (2) detecting the level of one or more biomarkers chosen from EFEMP2, SOCS2, and DCN, wherein a decreased level of EFEMP2, SOCS2, and/or DCN compared to a control value indicates the existence of endometrial cancer.

[0025] In a further embodiment, the present invention relates to an in vitro diagnostic method for the diagnosis of endometrial cancer comprising

(1) detecting the level of from 1 to 17 biomarker(s) chosen from P4HB, GMIP, IKBKE, FASTKD1, DDR1, SIRT6, PHKG2, ACAA1, AP1M2, EPS8L2, P2RX4, PPFIBP2, PPP1R16A, CGN, RASSF7, RNF183, and TJP3 in a sample from a patient wherein an increased level of said from 1 to 17 biomarkers compared to a control value indicates the existence of endometrial cancer and/or (2) detecting the level of from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN, wherein a decreased level of EFEMP2, SOCS2, and/or DCN compared to a control value indicates the existence of endometrial cancer.

[0026] In one embodiment, the in vitro diagnostic method comprises detecting the level of P4HB. In another embodiment, the in vitro diagnostic method comprises detecting the level of EFEMP2. In a further embodiment the in vitro method comprises detecting the level of IKBKE. In a further embodiment the in vitro diagnostic method comprises detecting the level of GMIP.

[0027] In accordance with the in vitro diagnostic method of the invention, the level of one or more of GMIP, IKBKE, or EFEMP2 may be detected in addition to P4HB. The in vitro diagnostic method may further comprise detecting the level of one or more of P4HB, IKBKE, or GMIP in addition to EFEMP2. The in vitro diagnostic method may further comprise detecting the level of one or more of GMIP, EFEMP2, or P4HB in addition to IKBKE. It is also envisaged that the in vitro diagnostic method may further comprise detecting the level of FASTKD1, DDR1, SIRT6, and/or PHKG2. The in vitro diagnostic method may further comprise detecting the level of from 1 to 12 biomarkers chosen from ACAA1, AP1M2, EPS8L2, P2RX4, PPFIBP2, PPP1R16A, CGN, RASSF7, RNF183, TJP3, SOCS2, and DCN.

[0028] In one embodiment, the patient has a risk factor for endometrial cancer or is being screened for endometrial cancer. Further, the sample from the patient may be (obtained) from a patient with abnormal uterine bleeding. In other words, the patient may suffer from abnormal uterine bleeding. The sample from said patient may also be (obtained) from a patient having an endometrium with increased thickness. The patient may, accordingly, have an endometrium with increased thickness.

[0029] The sample from the patient may be (obtained) from a pre-menopausal, peri-menopausal, or post-menopausal patient. Accordingly, the patient is a pre-menopausal, peri-menopausal, or post-menopausal patient. In one embodiment, the patient is pre-menopausal. In another embodiment, the patient is peri-menopausal. In a further embodiment, the patient is post-menopausal.

[0030] The sample may be a tissue sample, blood and/or serum, and/or uterine fluid. In one embodiment, the sample is a uterine fluid sample. The uterine fluid sample may be obtained by aspiration.

[0031] In one embodiment, the level of the biomarkers is determined with an antibody in accordance with the present invention. The level of the biomarker(s) may also be determined by RT-PCR.

[0032] The following markers may be detected in accordance with the in vitro diagnostic method of the present invention: P4HB, IKBKE, EFEMP2, SOCS2, FASTKD1, GMIP, DDR1, SIRT6, PHKG2, EPS8L2, PPP1R16A, P2RX4, RASSF7, and/or TJP3. Also the following markers may be detected in accordance with the in vitro diagnostic method of the present invention: P4HB, IKBKE, SOCS2, GMIP, DDR1, SIRT6, PHKG2, EPS8L2, PPP1R16A, P2RX4, RASSF7, and/or TJP3.

[0033] The markers to be detected may be P2RX4, P4HB, PHKG2, PPFIBP2, and/or SOCS2. The markers to be detected may also be P4HB, RASSF7, RNF183 and/or IKBKE.

[0034] In one embodiment, the in vitro diagnostic method comprises the detection of from 2 to 20 markers.

[0035] Preferably, the combination of the following markers is detected: P4HB, EFEMP2, SIRT6, GMIP, FASTKD1 and DDR1. Also preferred is the detection of a combination of the following markers: P4HB, EFEMP2, SIRT6, GMIP, FASTKD1 and PHKG2. Also preferred is the detection of a combination of the following markers: P4HB, EFEMP2, SIRT6, ACAA1, AP1M2, EPS8L2, IKBKE, P2RX4, PPFIBP2 and PPP1R16A.

[0036] The following marker combinations are also preferably detected in accordance with the present invention:

GMIP, IKBKE, PFHB, EFEMP2;

DDR1, FASTKD1, GMIP, IKBKE, P4HB, PHKG2, SIRT6, EFEMP2;

P4HB, EFEMP2, IKBKE, GMIP, FASTKD1.

[0037] In context of the present invention combinations of markers which include a combination with P4HB (i.e. set of markers including P4HB) are particularly preferred.

[0038] Also envisaged herein is the detection of the following combination of markers:

DDR1, FASTKD1, GMIP, IKBKE, P4HB, PHKG2, SIRT6, EFEMP2; SOCS2;

P4HB, SOCS2;

GMIP, IKBKE, P4HB, SOCS2;

GMIP, IKBKE, P4HB, SOCS2, FASTKD1;

GMIP, IKBKE, P4HB, SOCS2, DDR1;

GMIP, IKBKE, P4HB, SOCS2, PHKG2;

GMIP, IKBKE, P4HB, SOCS2, SIRT6;

GMIP, IKBKE, P4HB, SOCS2, ACAA1;

GMIP, IKBKE, P4HB, SOCS2, AP1M2;

GMIP, IKBKE, P4HB, SOCS2, EFEMP2;

GMIP, IKBKE, P4HB, SOCS2, EPS8L2;

GMIP, IKBKE, P4HB, SOCS2, P2RX4;

GMIP, IKBKE, P4HB, SOCS2, PPFIB2;

GMIP, IKBKE, P4HB, SOCS2, PPP1R16A;

GMIP, IKBKE, P4HB, SOCS2, ACAA1, FASTKD1;

GMIP, IKBKE, P4HB, SOCS2, FASTKD1, PHKG2;

GMIP, IKBKE, P4HB, SOCS2, FASTKD1, SIRT6;

GMIP, IKBKE, P4HB, SOCS2;

[0039] One or more additional biomarkers may be detected in accordance with the herein disclosed in vitro diagnostic method. The one or more additional biomarkers may be chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one embodiment, the one or more additional biomarkers are chosen from differential diagnosis biomarkers.

[0040] The one or more auxiliary biomarkers may be chosen from prognostic markers. The one or more auxiliary biomarkers may be chosen from endometrial cancer classification markers.

[0041] In a further embodiment, the present invention relates to a nucleic acid chosen from

IKBKE mRNA, cDNA, or a complement thereof; P4HB mRNA, cDNA, or a complement thereof; SOCS2 mRNA, cDNA, or a complement thereof; GMIP mRNA, cDNA, or a complement thereof; DDR1 mRNA, cDNA, or a complement thereof; EPS8L2 mRNA, cDNA, or a complement thereof; and PPP1R16A mRNA, cDNA, or a complement thereof, for use in diagnosing endometrial cancer.

[0042] The invention also relates to a nucleic acid chosen from

Primers for IKBKE;

Primers for P4HB;

Primers for SOCS2;

Primers for GMIP;

Primers for DDR1;

Primers for EPS8L2; and

Primers for PPP1R16A;

[0043] for use in diagnosing endometrial cancer.

[0044] In one embodiment, the invention relates to a nucleic acid chosen from

probe for IKBKE; probe for P4HB; probe for SOCS2; probe for GMIP; probe for DDR1; probe for EPS8L2; and probe for PPP1R16A, for use in diagnosing endometrial cancer.

[0045] Also a kit comprising two or more of the herein described probes for use in diagnosing endometrial cancer is envisaged in context of the present invention. Further, a kit comprising primers for two or more herein disclosed primers/primer pairs for use in diagnosing endometrial cancer is envisaged in context of the present invention.

[0046] In a further embodiment, the present invention relates to an antibody chosen from

an antibody to IKBKE; an antibody to P4HB; an antibody to SOCS2; an antibody to GMIP; an antibody to DDR1; an antibody to EPS8L2; and an antibody to PPP1R16A, for use in diagnosing endometrial cancer.

[0047] Accordingly, a kit comprising antibodies to two or more herein disclosed antibodies for use in diagnosing endometrial cancer is envisaged. The invention further relates to a kit for obtaining uterine fluid for use in diagnosing endometrial cancer by assessing the levels of from 1-20 biomarkers as defined and described herein.

[0048] The in vitro diagnostic method of the present invention may comprise determining/detecting the level of 2 biomarkers, 3 biomarkers, 4 biomarkers, 5 biomarkers, 7 biomarkers, 10 biomarkers, 15 biomarkers or 20 biomarkers.

[0049] In one embodiment, the present invention relates to an in vitro diagnostic method for diagnosing endometrial cancer comprising obtaining a uterine fluid aspirate sample from a patient having a symptom or risk factor for endometrial cancer and determining the level of from 1 to 100 biomarkers markers that are differentially expressed in endometrial cancer as compared to control values representative of individuals not affected by endometrial cancer, wherein (1) if the levels of 1 to 100 biomarkers are upregulated in the endometrial aspirate sample in the patient and in the control value then the patient has an increased likelihood of having endometrial cancer and wherein (2) if the level of the 1 to 100 biomarkers are downregulated in the aspirate sample and then the patient has an increased likelihood of having endometrial cancer.

[0050] The present invention further relates to a nucleic acid chosen from

ACAA1 mRNA, cDNA, or a complement thereof; AP1M2 mRNA, cDNA, or a complement thereof; CGN mRNA, cDNA, or a complement thereof; FASTKD1 mRNA, cDNA, or a complement thereof; P2RX4 mRNA, cDNA, or a complement thereof; RASSF7 mRNA, cDNA, or a complement thereof; RNF183 mRNA, cDNA, or a complement thereof; PHKG2 mRNA, cDNA, or a complement thereof; PPFIBP2 mRNA, cDNA, or a complement thereof, SIRT6 mRNA, cDNA, or a complement thereof, TJP3 mRNA, cDNA, or a complement thereof; EFEMP2 mRNA, cDNA, or a complement thereof; and DCN mRNA, cDNA, or a complement thereof, for use in diagnosing endometrial cancer.

[0051] Also subject of the present invention is a nucleic acid chosen from

Primers for ACAA1;

Primers for AP1M2;

Primers for CGN;

Primers for FASTKD1;

Primers for P2RX4;

Primers for RASSSF7;

Primers for RNF183;

Primers for SIRT6;

Primers for PPFIBP2;

Primers for PHKG2;

Primers for TJP3;

Primers for EFEMP2; and

Primers for DCN;

[0052] for use in diagnosing endometrial cancer.

[0053] In a further embodiment, the present invention relates to a nucleic acid chosen from

probe for ACAA1; probe for AP1M2; probe for CGN; probe for FASTKD1; probe for P2RX4; probe for RASSF7; probe for RNF183; probe for SIRT6; probe for PPFIBP2; probe for PKHG2; probe for TJP3; probe for EFEMP2; and probe for DCN, for use in diagnosing endometrial cancer.

[0054] In another embodiment, the invention relates to an antibody chosen from

an antibody to ACAA1; an antibody to AP1M2; an antibody to CGN; an antibody to FASTKD1; an antibody to P2RX4; an antibody to RASSF7; an antibody to RNF183; an antibody to SIRT6; an antibody to PPFIBP2; an antibody to PKHG2; an antibody to TJP3; an antibody to EFEMP2; and an antibody to DCN, for use in diagnosing endometrial cancer.

[0055] The antibody/antibodies, nucleic acid(s), probes, primer(s)/primer pair(s), and/or kit(s) described and defined herein are useful in the in diagnosis of endometrial cancer in accordance with the present invention. Therefore the antibody/antibodies, nucleic acid(s), probes, primer(s)/primer pair(s), and/or kit(s) described and defined herein are for use in diagnosing endometrial cancer. Similarly, also the use of the antibody/antibodies, nucleic acid(s), probes, primer(s)/primer pair(s), and/or kit(s) for the preparation of a diagnostic composition for diagnosing endometrial cancer is envisaged. Also a diagnostic composition for use in diagnosing endometrial cancer and comprising the herein described and defined antibody/antibodies, nucleic acid(s), probes, primer(s)/primer pair(s), and/or kit(s) is envisaged in context of the present invention.

[0056] Diagnosing endometrial cancer may, in this context, comprise or relate to a diagnostic method practised on the human or animal body which comprises or includes the features relating to

(i) the diagnosis for curative purposes stricto sensu representing the deductive medical or veterinary decision phase as a purely intellectual exercise, (ii) the preceding steps which are constitutive for making that diagnosis, and (iii) the specific interactions with the human or animal body which occur when carrying those out among these preceding steps which are of a technical nature.

[0057] In a further embodiment, the present invention relates to an in vitro diagnostic method for diagnosing endometrial cancer comprising providing or obtaining a uterine fluid sample from a human patient having a symptom or risk factor for a gynecological cancer and determining the level of RNA expression of from 2 to 9 biomarkers chosen from P4HB, EFEMP2, GMIP, IKBKE, DDR1, FASTKD1, SIRT6, PKHG2, and SOCS2 by quantitative PCR wherein an increased level of from 1 to 7 biomarkers chosen from P4HB, GMIP, IKBKE, DDR1, FASTKD1, SIRT6, and PKHG2 and/or a decreased level of EFEMP2 or SOCS2 as compared to control indicates the existence of endometrial cancer. Preferably, the gynecological cancer is endometrial cancer.

[0058] In one embodiment, the expression level of 2 to 8 biomarkers chosen from P4HB, EFEMP2, GMIP, IKBKE, DDR1, FASTKD1, SIRT6, and PKHG2 may be determined. The 2 to 8 biomarkers may also be chosen from P4HB, GMIP, IKBKE, DDR1, FASTKD1, SIRT6, PKHG2, and SOCS2.

[0059] The detection of the level may comprise contacting said one or more biomarkers with primers and reagents capable of amplifying specifically said one or more biomarkers and detecting the level of said amplified one or more biomarkers with a probe or probes that hybridize to said amplified biomarker. The probe hybrids specifically to said amplified biomarker.

[0060] The following combinations of biomarkers may, in particular, be detected in accordance with the method of the present invention: P4HB and EFEMP2; P4HB and IKBKE; P4HB and GMIP; EFEMP2 and IKBKE; EFEMP2 and P4HB; P4HB, GMIP, and IKBKE; P4HB, GMIP, and IKBKE.

[0061] Also the following combination of markers may be detected in accordance with the present method, wherein said combination comprises IKBKE and P4HB; IKBKE and SOCS2; P4HB and SOCS2; GMIP and IKBKE; GMIP and P4HB; GMIP and SOCS2; GMIP, SOCS2, and IKBKE; GMIP, SOCS2, and P4HB; GMIP, IKBKE, and P4HB; IKBKE, P4HB, and SOCS2; GMIP, IKBKE, P4HB, and SOCS2; GMIP, SOCS2, IKBKE, and EPS8L2; GMIP, SOCS2, P4HB, and EPS8L2; GMIP, IKBKE, P4HB, and EPS8L2; IKBKE, P4HB, SOCS2, and EPS8L2; GMIP, IKBKE, P4HB, SOCS2, and DDR1; GMIP, IKBKE, P4HB, SOCS2, EPS8L2, and PPP1R16A; GMIP, IKBKE, P4HB, SOCS2, PHKG2, and RASSF7; GMIP, IKBKE, P4HB, SOCS2, EPS8L2, and DDR1; GMIP, IKBKE, P4HB, SOCS2, EPS8L2, PPP1R16A, and DDR1; DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, RASSF7, SIRT6, TJP3, and SOCS2; or DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, RASSF7, SIRT6, TJP3, RNF183 and SOCS2.

[0062] Further, the following combination of markers may be detected in accordance with the present method, wherein said combination comprises GMIP, IKBKE, P4HB, SOCS2 and FASTKD1; GMIP, IKBKE, P4HB, SOCS2 and DDR1; GMIP, IKBKE, P4HB, SOCS2 and PHKG2; GMIP, IKBKE, P4HB, SOCS2 and SIRT6; GMIP, IKBKE, P4HB, SOCS2 and ACAA1; GMIP, IKBKE, P4HB, SOCS2 and EFEMP2; GMIP, IKBKE, P4HB, SOCS2 and EPS8L2; GMIP, IKBKE, P4HB, SOCS2 and P2RX4; GMIP, IKBKE, P4HB, SOCS2 and PPFIBP2; GMIP, IKBKE, P4HB, SOCS2 and PPP1R16A; GMIP, IKBKE, P4HB, SOCS2, ACAA1 and FASTKD1; GMIP, IKBKE, P4HB, SOCS2, PHKG2 and FASTKD1; GMIP, IKBKE, P4HB, SOCS2, SIRT6 and FASTKD1; ACAA1, AP1M2, EPS8L2, IKBKE, P2RX4, P4HB, PPFIBP2, PPP1R16A, SIRT6, and EFEMP2; GMIP, IKBKE, P4HB, and EFEMP2; DDR1, FASTKD1, PHKG2, SIRT6, SOCS2, GMIP, IKBKE, P4HB, and EFEMP2; DDR1, FASTKD1, PHKG2, SIRT6, GMIP, IKBKE, P4HB, and EFEMP2; or P4HB, EFEMP2, IKBKE, GMIP, and FASTKD1.

[0063] Further, the following combination of markers may be detected in accordance with the present method, wherein said combination comprises GMIP, IKBKE, P4HB, EFEMP2 and FASTKD1; GMIP, IKBKE, P4HB, EFEMP2 and DDR1; GMIP, IKBKE, P4HB, EFEMP2 and PHKG2; GMIP, IKBKE, P4HB, EFEMP2 and SIRT6; GMIP, IKBKE, P4HB, EFEMP2 and ACAA1; GMIP, IKBKE, P4HB, SOCS2 and EFEMP2; GMIP, IKBKE, P4HB, EFEMP2 and EPS8L2; GMIP, IKBKE, P4HB, EFEMP2 and P2RX4; GMIP, IKBKE, P4HB, EFEMP2 and PPFIBP2; GMIP, IKBKE, P4HB, EFEMP2 and PPP1R16A; GMIP, IKBKE, P4HB, EFEMP2, ACAA1 and FASTKD1; GMIP, IKBKE, P4HB, EFEMP2, PHKG2 and FASTKD1; or GMIP, IKBKE, P4HB, EFEMP2, SIRT6 and FASTKD1.

[0064] The methods of the present invention may further comprise providing a uterine fluid sample obtained from a patient with a pipelle device or syringe wherein the patient has a risk factor or symptom of endometrial cancer; contacting said sample with an agent capable of preserving, preventing, or lessening the degradation of RNA in said uterine fluid sample; determining in said sample the expression level of mRNA corresponding to from 1 to 20 herein described markers (preferably 2 to 8 markers) and one or more endogenous genes using quantitative PCR; normalizing the expression level of from 1 to 20 (preferably 2 to 8 markers) herein described biomarkers with the one or more endogenous genes; comparing the normalized level of the from 1 to 20 (preferably 2 to 8 markers) biomarkers to a control value wherein differential expression of from 1 to 20 (preferably 2 to 8 markers) of the biomarkers indicates endometrial cancer or an increased likelihood of endometrial cancer.

[0065] The present invention relates further to an in vitro diagnostic method comprising providing a uterine fluid sample obtained from a patient with a pipelle device or syringe wherein the patient has a risk factor or symptom of endometrial cancer; contacting said sample with an agent capable of preserving, preventing, or lessening the degradation of RNA in said uterine fluid sample; determining in said sample the expression level of mRNA corresponding to from 1 to 20 herein described markers (preferably 2 to 8 markers) and one or more endogenous genes using quantitative PCR; normalizing the expression level of from 1 to 20 (preferably 2 to 8 markers) herein described biomarkers with the one or more endogenous genes; comparing the normalized level of the from 1 to 20 (preferably 2 to 8 markers) biomarkers to a control value wherein differential expression of from 1 to 20 (preferably 2 to 8 markers) of the biomarkers indicates endometrial cancer or an increased likelihood of endometrial cancer.

[0066] The one or more endogenous genes may be chosen from POLR2A, B2M, PFN1, HMBS, G6PD, and PABPN1.

[0067] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising obtaining a sample from an individual and determining the level of from 1-17 biomarkers chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, and/or from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. In a specific aspect of this embodiment, when the level of from 1 to 17 biomarkers chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, are increased relative to a control value and/or the level from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN are decreased relative to control value then this indicates endometrial cancer or an increased chance of having endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to another aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0068] Amongst the biomarkers of Table 1, the levels of CGN, P4HB, PPP1R16A, IKBKE, RASSF7, RNF183, and TJP3, were found to have the highest mean level of overexpression in the RT-PCR studies as compared to their expression in normal samples (e.g., not having endometrial cancer). Thus, given that the RT-PCR experiments demonstrated a high level of overexpression in a statistically significant manner (all p-values are less than 0.0001 for the sample set studied) for these markers, they represent preferred markers for diagnosis of endometrial cancer and/or an increased likelihood of having endometrial cancer. Therefore, the levels of CGN, P4HB, PPP1R16A, IKBKE, RASSF7, RNF183, and TJP3 are excellent predictors of endometrial cancer and/or an increased likelihood of having endometrial cancer. The levels of these markers are less likely to give a false positive as compared to other markers whose expression levels are not as high and/or as significant. In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising obtaining a sample from an individual and determining the level of one or more biomarkers chosen from CGN, P4HB, PPP1R16A, IKBKE, RASSF7, RNF183, and TJP3 wherein if one or more of said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of cancer. Fingerprint patterns/expression profiles having from 1-7 biomarkers chosen from CGN, P4HB, PPP1R16A, IKBKE, RASSF7, RNF183, and TJP3 and from 1-13 biomarkers chosen from ACAA1, AP1M2, DDR1, EPS8L2, FASTKD1, GMIP, P2RX4, PHKG2, PPFIBP2, SIRT6, EFEMP2, SOCS2, and DCN, are one example of a set preferred profiles for diagnosing and/or predicting an increased likelihood of endometrial cancer. Specific examples of such profiles are described below. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0069] Amongst the biomarkers of Table 1, the level of some biomarkers were found to be able to differentiate samples from patients having cancer as compared to normal samples (or control) and samples from patients in the secretory phase of the menstrual cycle. Therefore, the levels of ACAA1, DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, RASSF7, SIRT6, TJP3, SOCS2, and DCN are excellent predictors of endometrial cancer in pre- and post-menopausal women and in peri-menopausal women, the levels of these markers are less likely to give a false positive as compared to other markers who expression level varies as a function of cycle. In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising obtaining a sample from an individual and determining the level of one or more biomarkers chosen from ACAA1, DDR1, EPS8L2, GMIP, IKBKE, LSR, P2RX4, P4HB, PHKG2, PPFIBP2, RASSF7, SIRT6, TJP3, SOCS2, and DCN wherein if one or more of said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. Fingerprint patterns/expression profiles having from 1-15 markers chosen from ACAA1, DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, SIRT6, TJP3, SOCS2, and DCN and from 1 to 5 markers chosen from AP1M2, CGN, FASTKD1, RNF183, and EFEMP2 are one example of a set preferred profiles for diagnosing and/or predicting an increased likelihood of endometrial cancer since the expression level of at least one of the markers in the profile does not vary as a function of menstrual cycle phase. Specific examples of such profiles are described below. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0070] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising obtaining a sample from an individual and determining the level of one or more biomarkers chosen from IKBKE, P4HB, SOCS2, GMIP, DDR1, EPS8L2, PPP1R16A, P2RX4, PHKG2, RASSF7, SIRT6, TJP3, AP1M2, RNF183, and DCN wherein if one or more of said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial and/or an increased likelihood of endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0071] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising obtaining a sample from an individual and determining the level of one or more biomarkers chosen from IKBKE, P4HB, SOCS2, GMIP, DDR1, EPS8L2, PPP1R16A, P2RX4, PHKG2, RASSF7, SIRT6, and TJP3, wherein if one or more of said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0072] In one embodiment of the invention, preferred biomarkers for diagnosing endometrial cancer and/or diagnosing an increased likelihood of endometrial cancer are IKBKE, P4HB, SOCS2, GMIP, DDR1, EPS8L2, and PPP1R16A. In one aspect, the level of the biomarker in primary tumor is determined. In one aspect, the level of the biomarker in blood, plasma, or serum is determined. In one aspect, the level of the biomarker uterine fluid is determined. Thus, the method according to this embodiment, comprise obtaining a sample and determining the level of from 1 to 7 biomarkers chosen from IKBKE, P4HB, SOCS2, GMIP, DDR1, EPS8L2, and PPP1R16A wherein differential expression of one or more of these biomarkers as compared to a control value indicates endometrial cancer and/or an increased risk of having endometrial cancer. In one aspect of this invention, the protein level of the biomarker is determined and/or estimated. In another aspect, the mRNA expression level is determined and/or estimated.

[0073] In one embodiment of the invention, preferred biomarkers for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer include GMIP, IKBKE, P4HB, RASSF7, DDR1, RNF183, EFEMP2 and SOCS2. GMIP, IKBKE, P4HB, RASSF7, DDR1, RNF183, EFEMP2 and SOCS2 were found to have excellent AUROC values and therefore are unexpectedly good classifiers in the sample set studied. In one aspect, the level of the biomarker in primary tumor is determined. In one aspect, the level of the biomarker in blood, plasma, or serum is determined. In one aspect, the level of the biomarker uterine fluid is determined. Thus, the method according to this embodiment, comprise obtaining a sample and determining the level of from 1 to 8 biomarkers chosen from GMIP, IKBKE, P4HB, RASSF7, DDR1, RNF183, EFEMP2 and SOCS2 wherein differential expression of one or more of these biomarkers as compared to a control value indicates endometrial cancer and/or an increased risk of having endometrial cancer. In one aspect of this invention, the protein level of the biomarker is determined and/or estimated. In another aspect, the mRNA expression level is determined and/or estimated.

[0074] In one embodiment of the invention, preferred biomarkers for diagnosing endometrial cancer and/or diagnosing an increased likelihood of endometrial cancer include P2RX4, P4HB, PHKG2, PPFIBP2 and SOCS2. As a result of these studies it was found that P2RX4, P4HB, PHKG2, PPFIBP2 and SOCS2 have excellent specificity for endometrial cancer diagnosis. In one aspect, the level of the biomarker in primary tumor is determined. In one aspect, the level of the biomarker in blood, plasma, or serum is determined. In one aspect, the level of the biomarker uterine fluid is determined. Thus, the method according to this embodiment, comprise obtaining a sample and determining the level of from 1 to 5 biomarkers chosen from P2RX4, P4HB, PHKG2, PPFIBP2 and SOCS2 wherein differential expression of one or more of these biomarkers as compared to a control value indicates endometrial cancer and/or an increased risk of having endometrial cancer. In one aspect of this invention, the protein level of the biomarker is determined and/or estimated. In another aspect, the mRNA expression level is determined and/or estimated.

[0075] In one embodiment of the invention, preferred biomarkers for diagnosing endometrial cancer and/or diagnosing an increased likelihood of endometrial cancer include IKBKE, P4HB, RASSF7, and RNF183. As a result of these studies it was found that IKBKE, P4HB, RASSF7, and RNF183 have excellent sensitivity for endometrial cancer diagnosis. In one aspect, the level of the biomarker in primary tumor is determined. In one aspect, the level of the biomarker in blood, plasma, or serum is determined. In one aspect, the level of the biomarker uterine fluid is determined. Thus, the method according to this embodiment, comprise obtaining a sample and determining the level of from 1 to 4 biomarkers chosen from IKBKE, P4HB, RASSF7, and RNF183 wherein differential expression of one or more of these biomarkers as compared to a control value indicates endometrial cancer and/or an increased risk of having endometrial cancer. In one aspect of this invention, the protein level of the biomarker is determined and/or estimated. In another aspect, the mRNA expression level is determined and/or estimated.

[0076] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising obtaining a sample from an individual and determining the level of from 2 to 7 biomarkers chosen from GMIP, IKBKE, P4HB, SOCS2, EPS8L2, PPP1R16A, and TJP3 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. As result of the studies disclosed herein, it was surprisingly found that combinations (e.g., profiles and/or fingerprint patterns) of biomarkers chosen from GMIP, IKBKE, P4HB, SOCS2, EPS8L2, PPP1R16A, and TJP3 have excellent sensitivity and specificity for endometrial cancer and the AUROC values for various combinations of these markers are indicative of the ability of these markers to separate patients having endometrial cancer from those not having endometrial cancer.

[0077] According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0078] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising obtaining a sample from an individual and determining the level of from 2 to 9 biomarkers chosen from GMIP, IKBKE, P4HB, SOCS2, EFEMP2, PHKG2, SIRT6, DDR1, and FASTKD1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. As result of the studies disclosed herein, it was surprisingly found that combinations (e.g., profiles and/or fingerprint patterns) of biomarkers chosen from GMIP, IKBKE, P4HB, SOCS2, EFEMP2, PHKG2, SIRT6, DDR1, and FASTKD1 have excellent sensitivity and specificity for endometrial cancer and the AUROC values for various combinations of these markers are indicative of the ability of these markers to separate patients having endometrial cancer from those not having endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined. In one specific aspect of this embodiment, the in vitro diagnostic method comprises providing a uterine fluid sample obtained from a patient with a pipelle device or syringe wherein the patient has a risk factor or symptom of endometrial cancer; contacting said sample with an agent capable of preserving, preventing, or lessening the degradation of RNA in said uterine fluid sample; determining in said sample the expression level of mRNA corresponding to said from 2 to 9 markers and one or more endogenous genes using quantitative PCR; normalizing the expression level of said from 2 to 9 biomarkers with the one or more endogenous genes; comparing the normalized level of the from 2 to 9 biomarkers to a control value wherein differential expression of from 2 to 9 of the biomarkers indicates endometrial cancer or an increased likelihood of endometrial cancer. In one specific aspect of this method, said one or more endogenous genes are chosen from POLR2A, B2M, PFN1, HMBS, G6PD, and PABPN1.

[0079] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising obtaining a sample from an individual and determining the level of from 2 to 8 biomarkers chosen from GMIP, IKBKE, P4HB, EFEMP2, PHKG2, SIRT6, DDR1, and FASTKD1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. As result of the studies disclosed herein, it was surprisingly found that combinations (e.g., profiles and/or fingerprint patterns) of biomarkers chosen from GMIP, IKBKE, P4HB, EFEMP2, PHKG2, SIRT6, DDR1, and FASTKD1 have excellent sensitivity and specificity for endometrial cancer and the AUROC values for various combinations of these markers are indicative of the ability of these markers to separate patients having endometrial cancer from those not having endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of 2 to 8 biomarkers are determined by quantitative PCR. In one specific aspect of this embodiment, the in vitro diagnostic method comprises providing a uterine fluid sample obtained from a patient with a pipelle device or syringe wherein the patient has a risk factor or symptom of endometrial cancer; contacting said sample with an agent capable of preserving, preventing, or lessening the degradation of RNA in said uterine fluid sample; determining in said sample the expression level of mRNA corresponding to said from 2 to 9 markers and one or more endogenous genes using quantitative PCR; normalizing the expression level of said from 2 to 8 biomarkers with the one or more endogenous genes; comparing the normalized level of the from 2 to 8 biomarkers to a control value wherein differential expression of from 2 to 8 of the biomarkers indicates endometrial cancer or an increased likelihood of endometrial cancer. In one specific aspect of this method, said one or more endogenous genes are chosen from POLR2A, B2M, PFN1, HMBS, G6PD, and PABPN1.

[0080] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising obtaining a sample from an individual and determining the level of from 2 to 8 biomarkers chosen from GMIP, IKBKE, P4HB, SOCS2, PHKG2, SIRT6, DDR1, and FASTKD1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. As result of the studies disclosed herein, it was surprisingly found that combinations (e.g., profiles and/or fingerprint patterns) of biomarkers chosen from GMIP, IKBKE, P4HB, SOCS2, PHKG2, SIRT6, DDR1, and FASTKD1 have excellent sensitivity and specificity for endometrial cancer and the AUROC values for various combinations of these markers are indicative of the ability of these markers to separate patients having endometrial cancer from those not having endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of 2 to 8 biomarkers are determined by quantitative PCR. In one specific aspect of this embodiment, the in vitro diagnostic method comprises providing a uterine fluid sample obtained from a patient with a pipelle device or syringe wherein the patient has a risk factor or symptom of endometrial cancer; contacting said sample with an agent capable of preserving, preventing, or lessening the degradation of RNA in said uterine fluid sample; determining in said sample the expression level of mRNA corresponding to said from 2 to 8 markers and one or more endogenous genes using quantitative PCR; normalizing the expression level of said from 2 to 8 biomarkers with the one or more endogenous genes; comparing the normalized level of the from 2 to 8 biomarkers to a control value wherein differential expression of from 2 to 8 of the biomarkers indicates endometrial cancer or an increased likelihood of endometrial cancer. In one specific aspect of this method, said one or more endogenous genes are chosen from POLR2A, B2M, PFN1, HMBS, G6PD, and PABPN1.

[0081] In one embodiment, the present invention provides a method for characterizing a sample obtained from a patient for prognostic, diagnostic and/or pharmacogenomic uses. Characterization of a sample obtained from a patient by determining the levels of one or more of the biomarkers of Table 1 can be used to provide information regarding diagnosis of endometrial cancer, disease progression, diagnosis of endometrial cancer type (and/or subtype), and selection of an appropriate therapeutic treatment. According to the method of the invention, a sample is obtained from an individual. The individual can be a healthy person, an individual diagnosed with cancer, an individual suspected of having cancer, an individual displaying one or more symptoms of cancer and/or an individual desiring screening for cancer. The method comprises the step of determining the level of the biomarker(s) of Table 1 in a sample obtained from a patient. Alternative methods for determining the biomarkers at the RNA and/or protein (IHC, mRNA expression analysis, etc) can be used in these methods. Detection of increased levels of from 1 to 17 the biomarkers of Table 1 that were found to be upregulated in endometrial cancer and/or detection of decreased levels of from 1 to 3 biomarkers that were found to be downregulated in endometrial cancer, compared to a control value, indicates that the patient has increased likelihood of having endometrial cancer.

[0082] In one embodiment, the invention provides a method for diagnosing a gynecological cancer comprising the use of diagnostic reagents for assaying for or detecting from 1 to 20 of the biomarkers listed in Table 1. In a more specific aspect of this embodiment, the diagnostic reagents are used for detecting the level of from 1 to 20 of the biomarkers listed in Table 1, for the diagnosis of endometrial cancer. In a more specific aspect of this embodiment, the diagnostic reagents are used for detecting the level of from 1 to 20 of the biomarkers listed in Table 1, for the detection of endometrial cancer. In one aspect of this embodiment, the level of the mRNA corresponding to from 1 to 20 biomarkers is determined. In one aspect of this embodiment, the level of the mRNA corresponding to from 2 to 17 biomarkers is determined. In one aspect of this embodiment, the level of the mRNA corresponding to from 3 to 15 biomarkers is determined. In one aspect of this embodiment, the level of a protein or polypeptide corresponding to from 1 to 20 biomarkers is determined. In one aspect of this embodiment, the level of a protein or polypeptide corresponding to from 2 to 17 biomarkers is determined. In one aspect of this embodiment, the level of a protein or polypeptide corresponding to from 3 to 15 biomarkers is determined. In one aspect of this embodiment, the sample that is analyzed is a tumor sample. In one aspect of this embodiment, the sample is analyzed is a uterine fluid sample. In one aspect of this embodiment, the sample that is analyzed is a serum, blood, or plasma sample. In one aspect, the sample is that is used is obtained by using a soft, straw-like device (pipelle) that is used to suction off a small sample of lining from the uterus (e.g., uterine fluid). In one aspect, the sample is obtained by using a sharp-edged tool called a curette by scraping a small sample and collecting it with a syringe or suction (e.g., dilation and curettage). In one aspect, the sample is obtained by using an electronic suction device (e.g., Vabra aspiration). In one aspect, the sample is obtained by using a spray of liquid (jet irrigation) to wash off some of the tissue that lines the uterus. In some aspects, a brush may be used to remove some of the lining before the washing is done. In one aspect, a blood, serum, or plasma sample is analyzed for from 1 to 20 of the biomarkers of the invention.

[0083] In microrarray studies, GMIP was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of GMIP was also found to be correlated in primary tumor and uterine fluid. Thus, GMIP is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having GMIP are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of GMIP and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, GMIP alone has AUROC value in Table 6 of 0.88 IKBKE alone has an AUROC value of 0.90, when these two markers are combined together in a profile the AUROC value 0.92 with a substantial increase in specificity (increased AUROC value indicate increased ability to separate the population). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0084] In microrarray studies, IKBKE was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of IKBKE was also found to be correlated in primary tumor and uterine fluid. Thus, IKBKE is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having IKBKE are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of IKBKE and from 2 to 19 biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, IKBKE alone has AUROC value in Table 6 of 0.90, P4HB alone has an AUROC value of 0.97, when these two markers are combined together in a profile the AUROC value 0.98 with a substantial increase in specificity to 100% (increased AUROC value indicate increased ability to separate the population). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0085] In microarray studies, EPS8L2 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.002 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of EPS8L2 was also found to be correlated in primary tumor and uterine fluid. Thus, EPS8L2 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having EPS8L2 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of EPS8L2 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, when EPS8L2 is combined with GMIP, IKBKE, P4HB, SOCS2, and DDR1 the AUROC value is 1 and the sensitivity is nearly 96% and the specificity is 100% (see Table 11). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0086] In microrarray studies, SOCS2 was found to be underexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of SOCS2 was also found to be correlated in primary tumor and uterine fluid. Thus, SOCS2 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having SOCS2 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of SOCS2 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, SOCS2 alone has AUROC value in Table 6 of 0.93, GMIP alone has an AUROC value of 0.88, when these two markers are combined together in a profile the AUROC value 0.999 with a substantial increase in sensitivity to 100% (increased AUROC value indicate increased ability to separate the population). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0087] In microrarray studies, EPS8L2 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.002 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of EPS8L2 was also found to be correlated in primary tumor and uterine fluid. Thus, EPS8L2 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having EPS8L2 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of EPS8L2 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, when EPS8L2 is combined with GMIP, IKBKE, P4HB, SOCS2, and DDR1 the AUROC value is 1 and the sensitivity is nearly 96% and the specificity is 100% (see Table 11). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0088] In microrarray studies, RASSF7 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0005 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of RASSF7 was also found to be correlated in primary tumor and uterine fluid. Thus, RASSF7 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having RASSF7 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of RASSF7 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, when RASSF7 is combined with DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, SIRT6, TJP3 and SOCS2 the AUROC value is 1 and the sensitivity is 100% and the specificity is 100% (see Table 11). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0089] In microrarray studies, DDR1 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.02 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of DDR1 was also found to be correlated in primary tumor and uterine fluid. Thus, DDR1 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having DDR1 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of DDR1 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, when DDR1 is combined with EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, SIRT6, TJP3, SOCS2, and RNF183 the AUROC value is 1 and the sensitivity is 100% and the specificity is 100% (see Table 11). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0090] In microrarray studies, PPP1R16A was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of PPP1R16A was also found to be correlated in primary tumor and uterine fluid. Thus, PPP1R16A is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having PPP1R16A are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of PPP1R16A and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, when PPP1R16A is combined with GMIP, IKBKE, P4HB, SOCS2, and EPS8L2 the AUROC value is nearly 1 and the sensitivity is nearly 92% and the specificity is 100% (see Table 11). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0091] In microrarray studies, PHKG2 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of PHKG2 was also found to be correlated in primary tumor and uterine fluid. Thus, PHKG2 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having PHKG2 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of PHKG2 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, when PHKG2 is combined with DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PPP1R16A, SIRT6, TJP3, SOCS2, and RNF183 the AUROC value is 1 and the sensitivity is 100% and the specificity is 100% (see Table 11). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0092] In microrarray studies, P2RX4 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0005 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of P2RX4 was also found to be correlated in primary tumor and uterine fluid. Thus, P2RX4 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having P2RX4 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of P2RX4 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, when P2RX4 is combined with DDR1, EPS8L2, GMIP, IKBKE, P4HB, PHKG2, PPP1R16A, SIRT6, TJP3, SOCS2, and RNF183 the AUROC value is 1 and the sensitivity is 100% and the specificity is 100% (see Table 11). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0093] In microrarray studies, ACAA1 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of ACAA1 was also found to be correlated in primary tumor and uterine fluid. Thus, ACAA1 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having ACAA1 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of ACAA1 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to one aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0094] In microrarray studies, AP1M2 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of AP1M2 was also found to be correlated in primary tumor and uterine fluid. Thus, AP1M2 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having AP1M2 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of AP1M2 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined.

[0095] In microrarray studies, CGN was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of CGN was also found to be correlated in primary tumor and uterine fluid. Thus, CGN is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having CGN are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of CGN and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined.

[0096] In microrarray studies, FASTKD1 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of FASTKD1 was also found to be correlated in primary tumor and uterine fluid. Thus, FASTKD1 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having FASTKD1 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of FASTKD1 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined.

[0097] In microrarray studies, PPFIBP2 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.02 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of PPFIBP2 was also found to be correlated in primary tumor and uterine fluid. Thus, PPFIBP2 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having PPFIBP2 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of PPFIBP2 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined.

[0098] In microrarray studies, RNF183 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of RNF183 was also found to be correlated in primary tumor and uterine fluid. Thus, RNF183 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having RNF183 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of RNF183 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, when RNF183 is combined with DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, SIRT6, TJP3, and SOCS2 the AUROC value is 1 and the sensitivity is 100% and the specificity is 100% (see Table 11). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined.

[0099] In microrarray studies, SIRT6 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of SIRT6 was also found to be correlated in primary tumor and uterine fluid. Thus, SIRT6 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having SIRT6 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of SIRT6 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, when SIRT6 is combined with DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, TJP3, SOCS2, and RNF183 the AUROC value is 1 and the sensitivity is 100% and the specificity is 100% (see Table 11). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined.

[0100] In microrarray studies, TJP3 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of TJP3 was also found to be correlated in primary tumor and uterine fluid. Thus, TJP3 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having TJP3 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of TJP3 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. For example, when TJP3 is combined with DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, SIRT6, SOCS2, and RNF183 the AUROC value is 1 and the sensitivity is 100% and the specificity is 100% (see Table 11). According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined.

[0101] In microrarray studies, EFEMP2 was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.0001 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of EFEMP2 was also found to be correlated in primary tumor and uterine fluid. Thus, EFEMP2 is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having EFEMP2 are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of EFEMP2 and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined.

[0102] In microrarray studies, DCN was found to be overexpressed in samples from patients having endometrial cancer as compared to normal values (non-affected). In RT-PCR studies this result was confirmed and a p-value of less than 0.005 was obtained for aspirate samples from non-affected individuals versus aspirates from individuals having endometrial cancer comparisons. The expression of DCN was also found to be correlated in primary tumor and uterine fluid. Thus, DCN is an excellent biomarker for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. Furthermore, fingerprint patterns/profiles having DCN are expected to be useful for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer. In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer comprising obtaining a sample from an individual and determining the level of DCN, and from 2 to 19 other biomarkers chosen from Table 1 wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined.

[0103] In one embodiment, the invention provide an in vitro diagnostic method for the diagnosis of endometrial cancer or an increased likelihood of endometrial comprising detecting the level of (1) from 1 to 17 biomarker(s) chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, and TJP3 in a sample from a patient wherein an increased level of said from 1 to 17 biomarkers compared to a control value indicates a diagnosis of endometrial cancer or increased likelihood of endometrial cancer and/or (2) detecting the level of from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN, wherein a decreased level of EFEMP2, SOCS2, and/or DCN compared to a control value indicates a diagnosis of endometrial cancer or increased likelihood of endometrial cancer. In one preferred aspect, the method of diagnosing endometrial cancer or an increased likelihood of endometrial cancer involves using one or more upregulated biomarkers and one or more downregulated biomarkers according to Table 1.

[0104] In one aspect of this embodiment, the patient has a risk factor for endometrial cancer or is being screened for endometrial cancer.

[0105] In one aspect of this embodiment, the sample from said patient is obtained from a patient with abnormal uterine bleeding.

[0106] In one aspect of this embodiment, the sample is from said patient is obtained from a patient having an endometrium with increased thickness.

[0107] In one aspect of this embodiment, the sample from said patient is obtained from a pre-menopausal, peri-menopausal, or post-menopausal patient.

[0108] In one aspect of this embodiment, the patient is pre-menopausal.

[0109] In one aspect of this embodiment, the patient is peri-menopausal.

[0110] In one aspect of this embodiment, the patient is post-menopausal.

[0111] In one aspect of this embodiment, the sample is chosen from a tissue sample, blood and/or serum, and uterine fluid.

[0112] In one aspect of this embodiment, the sample is a uterine fluid sample.

[0113] In one aspect of this embodiment, the uterine fluid sample is obtained by aspiration.

[0114] In one aspect of this embodiment, the level of the biomarker(s) is determined with an antibody.

[0115] In one aspect of this embodiment, the level of the biomarker(s) is determined by RT-PCR.

[0116] In one specific aspect, the level of the biomarker is determined by quantitative RT-PCR.

[0117] In one aspect of this embodiment, the markers are chosen from IKBKE, P4HB, SOCS2, GMIP, DDR1, EPS8L2, PPP1R16A, P2RX4, PHKG2, RASSF7, SIRT6, and TJP3.

[0118] In one aspect of this embodiment, the marker(s) is chosen from P2RX4, P4HB, PHKG2, PPFIBP2, and SOCS2.

[0119] In one aspect of this embodiment, the markers are chosen from P4HB, RASSF7, RNF183, and IKBKE.

[0120] In one aspect of this embodiment, from 2 to 20 markers are detected.

[0121] In one aspect of this embodiment, one or more additional auxiliary biomarkers are detected.

[0122] In one aspect of this embodiment, the one or more auxiliary biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and additional biomarkers for detecting endometrial cancer.

[0123] In one aspect of this embodiment, the one or more auxiliary biomarkers are chosen from differential diagnosis biomarkers.

[0124] In one aspect of this embodiment, the one or more auxiliary biomarkers are chosen from prognostic markers.

[0125] In one aspect of this embodiment, the one or more auxiliary biomarkers are chosen from endometrial cancer classification markers.

[0126] In one aspect of this embodiment, the invention provides a nucleic acid chosen from IKBKE mRNA, cDNA, or a complement thereof; P4HB mRNA, cDNA, or a complement thereof; SOCS2 mRNA, cDNA, or a complement thereof; GMIP mRNA, cDNA, or a complement thereof; DDR1 mRNA, cDNA, or a complement thereof; EPS8L2 mRNA, cDNA, or a complement thereof; and PPP1R16A mRNA, cDNA, complement thereof, for use for diagnosing endometrial cancer or an increased likelihood of having endometrial cancer.

[0127] In one aspect of this embodiment, the invention provides a nucleic acid chosen from ACAA1 mRNA, cDNA, or a complement thereof; AP1M2 mRNA, cDNA, or a complement thereof; CGN mRNA, cDNA, or a complement thereof; P2RX4 mRNA, cDNA, or a complement thereof; PPFIBP2 mRNA, cDNA, or a complement thereof;

[0128] RASSF7 mRNA, cDNA, or a complement thereof; TJP3 mRNA, cDNA, or a complement thereof; DCN mRNA, cDNA, or a complement thereof; and RNF183 mRNA, cDNA, or a complement thereof, for use for diagnosing endometrial cancer or an increased likelihood of having endometrial cancer.

[0129] In one aspect of this embodiment, the invention provides a nucleic acid chosen from EFEMP2 mRNA, cDNA, or a complement thereof; PHKG2 mRNA, cDNA, or a complement thereof; SIRT6 mRNA, cDNA, or a complement thereof; and FASTKD1 mRNA, cDNA, or a complement thereof, for use for diagnosing endometrial cancer or an increased likelihood of having endometrial cancer.

[0130] In one aspect of this embodiment, the invention provides primers chosen from primers for IKBKE; primers for P4HB; primers for SOCS2; primers for GMIP; primers for DDR1; primers for EPS8L2; and primers for PPP1R16A; for use for diagnosing endometrial cancer and/or an increased likelihood of having endometrial cancer.

[0131] In one aspect of this embodiment, the invention provides primers chosen from primers for ACAA1; primers for AP1M2; primers for CGN; primers for P2RX4; primers for PPFIBP2; primers for RASSF7; primers for RNF183; primers for TJP3; and primers for DCN; for use for diagnosing endometrial cancer and/or an increased likelihood of having endometrial cancer.

[0132] In one aspect of this embodiment, the invention provides primers chosen from primers for EFEMP2; primers for SIRT6; primers for PHKG2; and primers for FASTKD1; for use for diagnosing endometrial cancer and/or an increased likelihood of having endometrial cancer.

[0133] In one aspect of this embodiment, the invention provides a nucleic acid chosen from probe for IKBKE; probe for P4HB; probe for SOCS2; probe for GMIP; probe for DDR1; probe for EPS8L2; and probe for PPP1R16A,

for diagnosing endometrial cancer and/or an increased likelihood of having endometrial cancer.

[0134] In one aspect of this embodiment, the invention provides a nucleic acid chosen from probe for ACAA1; probe for AP1M2; probe for CGN; probe for P2RX4; probe for PPFIBP2; probe for RASSF7; probe for RNF183; probe for TJP3; and probe for DCN,

for diagnosing endometrial cancer and/or an increased likelihood of having endometrial cancer.

[0135] In one aspect of this embodiment, the invention provides a nucleic acid chosen from probe for EFEMP2; probe for FASTKD1; probe for SIRT6; probe for GMIP; and probe for PHKG2, for diagnosing endometrial cancer and/or an increased likelihood of having endometrial cancer.

[0136] In one aspect of this embodiment, the invention provides a kit comprising two or more probes to the 1-20 biomarkers of the invention, for diagnosing endometrial cancer and/or an increased likelihood of cancer.

[0137] In one aspect of this embodiment, the invention provides a kit comprising primers for two or more of the 1-20 biomarkers of the invention for diagnosing endometrial cancer and/or an increased likelihood of cancer.

[0138] In one aspect of this embodiment, the invention provides an antibody chosen from an antibody to IKBKE; an antibody to P4HB; an antibody to SOCS2; an antibody to GMIP; an antibody to DDR1; an antibody to EPS8L2; and

an antibody to PPP1R16A, for diagnosing endometrial cancer and/or an increased likelihood of having endometrial cancer.

[0139] In one aspect of this embodiment, the invention provides an antibody chosen from an antibody to ACAA1; an antibody to AP1M2; an antibody to CGN; an antibody to P2RX4; an antibody to PPFIBP2; an antibody to RASSF7; an antibody to RNF183; an antibody to TJP3; and an antibody to DCN, for diagnosing endometrial cancer and/or an increased likelihood of having endometrial cancer.

[0140] In one aspect of this embodiment, the invention provides an antibody chosen from an antibody to EFEMP2; an antibody to FASTKD1; an antibody to SIRT6; an antibody to GMIP; and an antibody to PHKG2; for diagnosing endometrial cancer and/or an increased likelihood of having endometrial cancer.

[0141] In one aspect of this embodiment, the invention provides a kit comprising antibodies to two or more biomarkers of Table 1 for diagnosing endometrial cancer and/or an increased likelihood of cancer.

[0142] In aspect of this embodiment, the invention provides a kit for obtaining uterine fluid for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer by assessing the levels of from 1-20 biomarkers of Table 1.

[0143] In one aspect of this embodiment, the in vitro diagnostic method comprises determining the level of 2 biomarkers of the invention. In one aspect of this embodiment, the in vitro diagnostic method comprises determining the level of 3 biomarkers of the invention. In one aspect of this embodiment, the in vitro diagnostic method comprises determining the level of 4 biomarkers of the invention. In one aspect of this embodiment, the in vitro diagnostic method comprises determining the level of 5 biomarkers of the invention. In one aspect of this embodiment, the in vitro diagnostic method comprises determining the level of 5 biomarkers of the invention. In one aspect of this embodiment, the in vitro diagnostic method comprises determining the level of 7 biomarkers of the invention. In one aspect of this embodiment, the in vitro diagnostic method comprises determining the level of 10 biomarkers of the invention. In one aspect of this embodiment, the in vitro diagnostic method comprises determining the level of 15 biomarkers of the invention. In one aspect of this embodiment, the in vitro diagnostic method comprises determining the level of 20 biomarkers of the invention.

[0144] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

[0145] Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0146] FIG. 1 shows correlation of the expression level of biomarkers in primary tumor and in uterine fluid for the biomarkers including those of the invention. See Example 3 for details.

[0147] FIGS. 2A and 2B is a box and whiskers plots represent the relative amount of RNA (RQ) present in the aspirate samples from patients having endometrial cancer as compared with the control samples for each gene as determined by RT-PCR. 30 tumor samples and 24 controls were considered in the plots. Boxes represent the interquartile range for each gene and the whiskers go from percentile 10 to 90 of the RQ values for each gene. The bar in the boxes represents the median RQ. The white boxes represent the values for the tumour samples of each gene and the shaded boxes the values for the control samples. See Example 4 for details.

[0148] FIG. 3 shows an example of the expression level of RNF183 as determined by RT-PCR in aspirates obtained from patients having endometrial cancer (RNF183_T), normals in secretory phase (RNF183_S), normals not having endometrial cancer (RNF183_N), and all normals together (RNF183_Nt).

[0149] FIG. 4 shows an example of the expression level of AP1M2 as determined by RT-PCR in aspirates obtained from patients having endometrial cancer (AP1M2_T), normals in secretory phase (AP1M2_S), normals not having endometrial cancer (AP1M2_N), and all normals together (AP1M2_Nt).

[0150] FIG. 5 shows an example of the expression level of CGN as determined by RT-PCR in aspirates obtained from patients having endometrial cancer (CGN_T), normals in secretory phase (CGN_S), normals not having endometrial cancer (CGN_N), and all normals together (CGN_Nt).

[0151] FIG. 6 shows an example of the expression level of FASTKD1 as determined by RT-PCR in aspirates obtained from patients having endometrial cancer (FASTKD1_T), normals in secretory phase (FASTKD1_S), normals not having endometrial cancer (FASTKD1_N), and all normals together (FASTKD1_Nt).

[0152] FIG. 7 shows an example of the expression level of IKBKE as determined by RT-PCR in aspirates obtained from patients having endometrial cancer (IKBKE_T), normals in secretory phase (IKBKE_S), normals not having endometrial cancer (IKBKE_N), and all normals together (IKBKE_Nt).

[0153] FIG. 8 shows an example of the expression level of P4HB as determined by RT-PCR in aspirates obtained from patients having endometrial cancer (P4HB_T), normals in secretory phase (P4HB_S), normals not having endometrial cancer (P4HB_N), and all normals together (P4HB_Nt).

[0154] FIG. 9 shows an example of the expression level of SOCS2 as determined by RT-PCR in aspirates obtained from patients having endometrial cancer (SOCS2_T), normals in secretory phase (SOCS2_S), normals not having endometrial cancer (SOCS2_N), and all normals together (SOCS2_Nt).

[0155] FIG. 10 shows a western blot of endometrial cancer tissue with antibody against a Biomarker of the invention: P4HB. The samples tested include four normal tissues (N) and four tumor tissues (T). Normal and tumors tissues were obtained from the same patient. As a positive control: total protein extract from the endometrial tumour cell line Isikawa. See Example 6.

[0156] FIG. 11 shows a western blot of endometrial cancer tissue with antibody against a Biomarker of the invention: AP1M2. The samples tested include four normal tissues (N) and four tumor tissues (T) from 4 different patients. Matched normal and tumors tissues were obtained from the same patient. As a positive control: total protein extract from the endometrial tumor cell line Isikawa. See Example 6.

[0157] FIG. 12 shows a western blot of endometrial cancer tissue with antibody against a Biomarker of the invention: IKBKE. The samples tested include a normal tissue (N) and a tumor tissue (T). Matched normal and tumors tissue were obtained from the same patient. As a positive control: total protein extract from the endometrial tumor cell line Isikawa. See Example 6.

[0158] FIG. 13 shows a western blot of endometrial cancer tissue with antibody against a Biomarker of the invention: EPS8L2. The samples tested include 3 normal tissues (N) and 3 tumor tissues (T) from 3 different patients. As a positive control: total protein extract from the endometrial tumor cell line. Matched normal and tumors tissues were obtained from the same patient. See example 6.

[0159] FIG. 14 shows a western blot of endometrial cancer tissue with antibody against a Biomarker of the invention: DDR1. The samples tested include a normal tissue (N) and a tumor tissue (T). Matched normal and tumors tissue were obtained from the same patient. As a positive control: total protein extract from the endometrial tumor cell line Isikawa. See Example 6.

[0160] FIG. 15 shows a western blot of endometrial cancer tissue with antibody against a Biomarker of the invention: CGN. The samples tested include four normal tissues (N) and four tumor tissues (T) from four different patients. Matched normal and tumors tissues were obtained from the same patient. As a positive control: total protein extract from the endometrial tumor cell line Isikawa. See Example 6.

[0161] FIG. 16 shows a western blot of endometrial cancer tissue with antibody against a Biomarker of the invention: TJP3. The samples tested include a normal tissue (N) and a tumor tissue (T). Matched normal and tumors tissue were obtained from the same patient. As a positive control: total protein extract from the endometrial tumor cell line Isikawa. See Example 6.

[0162] FIG. 17 shows the calculated risk of cancer using 48 non-tumor samples and 33 tumor samples using the ACAA1, AP1M2, EPS8L2, IKBKE, P2RX4, P4HB, PPFIBP2, PPP1R16A, SIRT6, EFEMP2. See Example 5.

[0163] FIG. 18 shows the calculated risk of cancer using 48 non-tumor samples and 33 tumor samples using the FASTKD1, GMIP, P4HB, EFEMP2, SIRT6, and PHKG2. See Example 5.

[0164] FIG. 19 shows the calculated risk of cancer using 48 non-tumor samples and 33 tumor samples using the FASTKD1, GMIP, P4HB, EFEMP2, DDR1, and SIRT6. See Example 5.

DETAILED DESCRIPTION OF THE INVENTION

[0165] The present invention is based on the finding of the association of alterations in the mRNA expression levels of the biomarkers listed in Table 1 in samples from patients having endometrial cancer as compared to control values (e.g., normal tissue (non-affected) or value). These biomarkers therefore represent endometrial cancer biomarkers. Additionally, the inventors surprisingly found that samples obtained from uterine fluid of endometrial cancer patients display expression profiles for the biomarkers listed in Table 1 that were generally correlated to the expression profiles from the primary tumor. Furthermore, a number of the markers found by the inventors are expected to be found on cell surfaces and/or in blood as blood based markers (or in other body fluids like uterine fluid). As shown in Example 6, the upregulated biomarkers of Table 1 were shown to be overexpressed at the protein level in primary tissue as compared to normal non-affected tissue. For example, the protein level of P4HB by western blot analysis, revealed that this biomarker is overexpressed at a protein level as well. FIG. 11 through FIG. 16 show overexpression, at the protein level, of AP1M2, IKBKE, EPS8L2, DDR1, CGN, and TJP3. Furthermore, P4HB, PPP1R16A and EPS8L2 presented a specific cytoplasmatic expression within the tumoral cells in all carcinoma histological types and grades, and an absence or faint cytoplasmatic staining within the normal epithelial glands as determined by tissue microarray (TMA) immunohistochemistry (IHC).

[0166] These studies provide endometrial cancer diagnostic biomarkers with excellent predictive value, alone or in combinations, that may be detected using methods which are less invasive as compared to the current standard of care. Furthermore, the inventors have identified specific subsets of biomarkers that are capable of distinguishing, in endometrial aspirates samples, endometrial cancer affected patients from different sub-groups of non-affected patients.

[0167] Several of the studies used to identify (expression microarray) and validate (RT-PCR) the biomarkers of the invention are described briefly below and in more detail in the Example section.

[0168] More specifically, the inventors performed gene expression analysis on expression microarrays to detect genes that are differentially expressed in endometrial cancer as compared to normal tissues. The gene expression microarray studies disclosed herein revealed that a number of genes in endometrial cancer samples were overexpressed as compared to normal endometrial tissue. It was found that ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, and TJP3, were overexpressed in endometrial cancer samples and EFEMP2, SOCS2, and DCN were underexpressed, as compared to their respective levels in normal endometrial tissue using a microarray experimental strategy. These results are summarized in Table 1 which has the common abbreviation for the gene, the ENSMBL accession numbers (corresponding to the gene, transcript(s), and protein related to the biomarkers of the invention), the fold change values and the p-values for statistical significance.

TABLE-US-00001 TABLE 1 Differential expression of endometrial cancer biomarkers in primary tumor as compared to control values (obtained from a pool of unaffected tissue, see Example 1). Array data Name gene Transcrip Protein Fold change p-value RASSF7 ENSG00000099849 ENST00000397583 ENSP00000380713 1.94 0.07 ENST00000397582 ENSP00000380712 CGN ENSG00000143375 ENST00000271636 ENSP00000271636 1.79 0.22 AP1M2 ENSG00000129354 ENST00000250244 ENSP00000250244 1.71 0.11 PHKG2 ENSG00000156873 ENST00000328273 ENSP00000329968. 1.34 0.09 PPP1R16A ENSG00000160972 ENST00000292539 ENSP00000292539 1.44 0.10 DDR1 ENSG00000137332 ENST00000259875 ENSP00000259875 1.93 0.13 ENST00000400414 ENSP00000383265 ENST00000400411 ENSP00000383262 ENST00000383377 ENSP00000372868 ENST00000400410 ENSP00000383261 P4HB ENSG00000185624 ENST00000331483 ENSP00000327801 1.90 0.13 RNF183 ENSG00000165188 ENST00000297894 ENSP00000297894 1.73 0.19 IKBKE ENSG00000143466 ENST00000367120 ENSP00000356087 1.37 0.17 EPS8L2 ENSG00000177106 ENST00000318562 ENSP00000320828 1.34 0.20 TJP3 ENSG00000105289 ENST00000262968 ENSP00000262968 1.57 0.17 ENST00000382008 ENSP00000371438 SIRT6 ENSG00000077463 ENST00000269860 ENSP00000269860 1.27 0.15 ENST00000305232 ENSP00000305310 ENST00000337491 ENSP00000337332 ENST00000381935 ENSP00000371360 GMIP ENSG00000089639 ENST00000203556 ENSP00000203556 1.42 0.05 ACAA1 ENSG00000060971 ENST00000333167 ENSP00000333664 1.26 0.11 ENST00000301810 ENSP00000301810 ENST00000358122 ENSP00000350838 FASTKD1 ENSG00000138399 ENST00000260971 ENSP00000260971 1.71 0.06 ENST00000361619 ENSP00000354598 ENST00000361819 ENSP00000354821 DCN ENSG00000011465 ENST00000052754 ENSP00000052754 -2.55 0.06 ENST00000228329 ENSP00000228329 ENST00000303320 ENSP00000302031 ENST00000350856 ENSP00000308451 SOCS2 ENSG00000120833 ENST00000340600 ENSP00000339428 -1.69 0.06 ENST00000393123 ENSP00000376831 EFEMP2 ENSG00000172638 ENST00000307998 ENSP00000309953 -1.22 0.08 P2RX4 ENSG00000135124 ENST00000337233 ENSP00000336607 1.70 0.12 ENST00000359949 ENSP00000353032 PPFIBP2 ENSG00000166387 ENST00000299492 ENSP00000299492 1.52 0.11

[0169] As shown in FIG. 1, it was found that the markers of Table 1 were also found to be differentially expressed in samples obtained from uterine fluid in patients having endometrial cancer. Markers which were not highly correlated fall off or further away from the correlation line in FIG. 1.

[0170] The overexpression of ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, and TJP3, and the underexpression of DCN, SOCS2, and EFEMP2 in endometrial cancer was validated by RT-PCR using an independent set of samples. The samples used in this study were obtained from uterine fluid of individuals having endometrial cancer and from patients not having endometrial cancer. These results are summarized in Table 2 and illustrated in FIG. 2A and FIG. 2B. These results demonstrate that these markers displayed statistically significant differential expression in endometrial cancer samples in samples from individuals having endometrial cancer as compared to normal individuals and/or samples (e.g., control value).

TABLE-US-00002 TABLE 2 Differential expression of biomarkers in aspirate samples from patients having endometrial cancer compared to aspirates from patients not having endometrial cancer. Mean RQ SEM p value ACAA1 1.472 0.476 <0.0001 AP1M2 1.688 0.422 <0.0001 CGN 2.348 1.312 <0.0001 DCN 0.246 0.196 0.002 DDR1 1.515 0.534 0.0167 EFEMP2 0.414 0.289 <0.0001 EPS8L2 1.646 0.559 0.0016 FASTKD1 1.693 0.662 <0.0001 GMIP 1.338 0.491 <0.0001 IKBKE 2.877 1.617 <0.0001 P2RX4 1.544 0.504 0.0002 P4HB 1.998 0.647 <0.0001 PHKG2 1.557 0.378 <0.0001 PPFIBP2 1.540 0.725 0.0094 PPP1R16A 1.915 0.789 <0.0001 RASSF7 1.848 0.770 0.0001 RNF183 3.648 2.368 <0.0001 SIRT6 1.611 0.550 <0.0001 SOCS2 0.265 0.177 <0.0001 TJP3 2.088 0.928 <0.0001 The p-values were calculated using a non-parametic Mann-Whitney test. Mean RQ refers to relative quantity, and SEM refers to standard error of the mean.

[0171] The finding of the correlation of expression levels of these biomarkers in primary tissue and uterine fluid was surprising given the heterogeneity of uterine fluid and the findings in the initial microarrays studies. It is believed that this is the first time that that the levels of biomarkers in primary endometrial cancer were shown to be correlated in a statistically significant manner to those found in uterine fluid and therefore this provides a less invasive and more standardized method of screening for endometrial cancer and/or an increased risk of endometrial cancer. The invention therefore provides a method for diagnosing endometrial cancer and/or an increased likelihood of endometrial cancer by obtaining a uterine fluid sample and determining the level of biomarkers differentially expressed in endometrial cancer as compared to control value. In one aspect, the uterine fluid sample is obtained by aspiration. In one aspect, the uterine fluid sample is obtained gently washing and/or rinse the uterine cavity. In one aspect, the level of mRNA is determined. In one aspect, the level of protein is determined. In one aspect, the biomarkers are chosen from the 20 listed in Table 1.

[0172] Surprisingly, the p-values for the individual biomarkers in Table 1 as determined in the microarray studies with one sample set were significantly improved upon when the same biomarkers were analyzed by a different technique (quantitative RT-PCR) using a different set of samples, obtained from the patient by a different method. In general the p-values were over 100 fold improved compared to the microarray studies.

[0173] The inventors have found that individually each of the biomarkers of Table 1 have predictive value for the diagnosis of endometrial cancer. Furthermore, combinations of these biomarkers have additional predictive value for the diagnosis of endometrial cancer. For example, the inventors have surprisingly found that numerous sub-groups of the biomarkers of Table 1 having from 2-20 biomarkers in various combinations give fingerprint patterns having excellent predictive value for diagnosis or detection of endometrial cancer. Additionally, the inventors have also contemplate that addition of other biomarkers besides those listed in Table 1, to the fingerprint pattern also can increase predictive value, and can be useful for classifying endometrial cancers, for differential diagnosis of diseases other than endometrial cancer, and for endometrial cancer prognosis.

[0174] In one embodiment, the present invention provides a method for characterizing a sample obtained from a patient for prognostic, diagnostic and/or pharmacogenomic uses. Characterization of the a sample obtained from a patient according to the levels one or more of the biomarkers of Table 1 can be used to provide information regarding disease progression, diagnosis of endometrial cancer type (and/or subtype), and selection of an appropriate therapeutic treatment. According to the method of the invention, a sample is obtained from an individual. The individual can be a healthy person, an individual diagnosed with cancer, an individual suspected of having cancer, an individual displaying one or more symptoms of cancer and/or an individual desiring screening for cancer. The method comprises the step of determining the level of the biomarker(s) of Table 1 in a sample obtained for a patient. Alternative methods for determining the biomarkers (IHC, mRNA expression analysis, etc) can be used in these methods.

[0175] In one embodiment, the invention provides a method for diagnosing endometrial cancer and/or an increased likelihood of having endometrial cancer which comprises obtaining a sample from an individual and determining the level of from 1 to 20 biomarkers of Table 1 in the sample. If the level of from 1 to 17 of the upregulated biomarkers are increased relative to control value and/or the level of from 1 to 3 of the downregulated markers are decreased compared to control value, then the patient has an increased likelihood of having endometrial cancer.

[0176] In one embodiment, the invention provides a method for diagnosing endometrial cancer which comprises obtaining a sample from a patient having a symptom of endometrial cancer and determining the level of from 1 to 20 biomarkers of Table 1 in the sample. In one aspect of this embodiment, the symptom of endometrial cancer is chosen from vaginal bleeding and/or spotting in postmenopausal women, abnormal uterine bleeding, abnormal menstrual periods, bleeding between normal periods in premenopausal women in women older than 40, extremely long, heavy, or frequent episodes of bleeding, anemia caused by chronic loss of blood, lower abdominal pain or pelvic cramping, thin white or clear vaginal discharge in postmenopausal women, and suspect symptoms in peri-menopausal. Thus, in one aspect of this embodiment, the invention relates to a method for diagnosing endometrial cancer comprising obtaining or providing a sample from an individual having vaginal bleeding and/or spotting in postmenopausal women, abnormal uterine bleeding, abnormal menstrual periods, bleeding between normal periods in premenopausal women in women older than 40, extremely long, heavy, or frequent episodes of bleeding, anemia caused by chronic loss of blood, lower abdominal pain or pelvic cramping, thin white or clear vaginal discharge in postmenopausal women, or suspect symptoms in peri-menopausal and determining the level of from 1-17 biomarkers chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, and/or from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. In a specific aspect of this embodiment, when the level of from 1 to 17 biomarkers chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, are increased relative to a control value and/or the level from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN are decreased relative to control value then this indicates endometrial cancer or an increased chance of having endometrial cancer. According to one aspect of this embodiment, the levels of the one or more biomarkers for detecting endometrial cancer are normalized to one or more endogenous biomarkers or genes. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to another aspect of this embodiment, the level of protein corresponding to the biomarker is determined.

[0177] In one embodiment, the invention provides a method for diagnosing endometrial cancer which comprises obtaining a sample from a patient having a risk factor for endometrial cancer and determining the level of from 1 to 20 biomarkers of Table 1 in the sample. In one aspect of this embodiment, the risk factor for endometrial cancer is chosen from high levels of estrogen, endometrial hyperplasia, obesity, hypertension, polycystic ovary syndrome, nulliparity, infertility, early menarche, late menopause, endometrial polyps or other benign growths of the uterine lining, diabetes, tamoxifen exposure, hyperplasia, high intake of animal fat, pelvic radiation therapy, breast cancer, ovarian cancer, heavy daily alcohol consumption, family history of cancer, family history of HNPCC, and being an HNPCC mutation carrier. In one aspect of this embodiment, the biomarkers are selected for distinguishing patients having tumor from those in secretory phase of the menstrual cycle. Thus, in one aspect of this embodiment, the invention relates to a method for diagnosing endometrial cancer comprising obtaining or providing a sample from an individual having a risk factor for cancer which is high levels of estrogen, endometrial hyperplasia, obesity, hypertension, polycystic ovary syndrome, nulliparity, infertility, early menarche, late menopause, endometrial polyps or other benign growths of the uterine lining, diabetes, tamoxifen exposure, hyperplasia, high intake of animal fat, pelvic radiation therapy, breast cancer, ovarian cancer, heavy daily alcohol consumption, family history of cancer, family history of HNPCC, or being an HNPCC mutation carrier which is and determining the level of from 1-17 biomarkers chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, and/or from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. In a specific aspect of this embodiment, when the level of from 1 to 17 biomarkers chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, are increased relative to a control value and/or the level from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN are decreased relative to control value then this indicates endometrial cancer or an increased chance of having endometrial cancer. According to one aspect of this embodiment, the levels of the one or more biomarkers for detecting endometrial cancer are normalized to one or more endogenous biomarkers or genes. According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to another aspect of this embodiment, the level of protein corresponding to the biomarker is determined. In a preferred aspect of this embodiment, the method involves determining the level of from 1-17 upregulated biomarkers of Table 1 and from 1-3 downregulated markers of Table 1 by quantitative PCR in a uterine fluid sample.

[0178] In one embodiment, the invention provides a method for diagnosing endometrial cancer which comprises obtaining a sample from a patient having an endometrium with an increased thickness. In one aspect of this embodiment, the thickness of the endometrium is measured by transvaginal ultrasound. "Increased thickness" refers a thickness above a value common employed in the art to identify patients that warrant further work-up or investigation. The method of this embodiment involves determining the level determining the level of from 1 to 20 biomarkers of Table 1 in a sample obtained from a patient having an endometrium of increased thickness. According to an aspect of this embodiment, the sample is a uterine fluid sample. In another aspect of this embodiment, the level of from 1-20 mRNA biomarkers is determined. In another aspect of this embodiment, the level of from 1-20 protein biomarkers is determined. In one aspect of this embodiment, the biomarkers are chosen from those that are capable of distinguishing samples from endometrial cancer affected patients and from those patients having another condition that increases the thickness of the endometrium. Conditions that increases the thickness of the endometrium but are not necessarily present in endometrial cancer patients include, but are not limited to, tamoxifen exposure, exposure to hormones, phase of menstrual cycle (in general the endometrium thickness increase in going from proliferative to secretory phase). Some preferred biomarkers which performed well in separating samples from patients affected with endometrial cancer from non-endometrial cancer affected patients in the secretory phase are shown in Table 9 in the Examples. Thus, in one aspect of this embodiment, the invention relates to a method for diagnosing endometrial cancer comprising obtaining or providing a sample from an individual having increased endometrial thickness and determining the level of from 1-17 biomarkers chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, and/or from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN wherein if said markers are differentially expressed compared to a control value, then the individual is diagnosed with endometrial cancer and/or an increased likelihood of endometrial cancer. In a specific aspect of this embodiment, when the level of from 1 to 17 biomarkers chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, are increased relative to a control value and/or the level from 1 to 3 biomarkers chosen from EFEMP2, SOCS2, and DCN are decreased relative to control value then this indicates endometrial cancer or an increased chance of having endometrial cancer. According to one aspect of this embodiment, the levels of the one or more biomarkers for detecting endometrial cancer are normalized to one or more endogenous biomarkers or genes.

[0179] According to one aspect of this embodiment, the sample is chosen from a tissue sample and a fluid sample. In one aspect, the fluid sample is a uterine fluid sample or uterine aspirate. According to one aspect of this embodiment, the level of mRNA corresponding to the biomarker is determined. According to another aspect of this embodiment, the level of protein corresponding to the biomarker is determined. In a preferred aspect of this embodiment, the method involves determining the level of from 1-17 upregulated biomarkers of Table 1 and from 1-3 downregulated markers of Table 1 by quantitative PCR in a uterine fluid sample.

[0180] Profiles, Fingerprint Patterns, and Combinations

[0181] The initial microarray studies disclosed herein demonstrated that each of the biomarkers of Table 1, as independent biomarkers, have predictive value for diagnosing endometrial cancer. Furthermore, it was found that combinations of markers (e.g., profiles or fingerprint patterns) have increased predictive value for endometrial cancer. Thus, in addition to using these markers as individual markers, they can be used in combinations of 2 to 20 biomarkers for diagnosing endometrial cancer. In some embodiments additional markers can be included in the profile or fingerprint pattern for differential diagnostic purposes (exclude or confirm a disease or conditions other than endometrial cancer (e.g., endometrial hyperplasia, endometrosis, ovarian cancer, fibroids, etc.)), classification of type of endometrial cancer (e.g., type I versus type II), classification of cell type of endometrial cancer, and prognosis.

[0182] In one embodiment, the invention provides for profiles and/or fingerprint patterns having 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, of the biomarkers of Table 1. In one aspect of this embodiment, the level of mRNA corresponding to the biomarkers in the profile is determined for use in diagnosis endometrial cancer and/or an increased likelihood of endometrial cancer. In one aspect of this embodiment, the level of protein corresponding to the biomarkers in the profile is determined for use in diagnosis endometrial cancer and/or an increased likelihood of endometrial cancer. In one aspect of this embodiment, the level of the biomarkers is determined in a sample obtained from uterine fluid. In one aspect of this embodiment, the level of the biomarkers is determined in a sample obtained from serum, blood, or plasma.

[0183] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of an ACAA1 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from AP1M2, CGN,

DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. Combinations or subcombinations including ACAA1 are ACAA1 and AP1M2; ACAA1 and CGN; ACAA1 and DDR1; ACAA1 and EPS8L2; ACAA1 and FASTKD1; ACAA1 and GMIP; ACAA1 and IKBKE; ACAA1 and P2RX4; ACAA1 and P4HB; ACAA1 and PHKG2; ACAA1 and PPFIBP2; ACAA1 and PPP1R16A; ACAA1 and RASSF7; ACAA1 and RNF183; ACAA1 and SIRT6; ACAA1 and TJP3; ACAA1 and EFEMP2; ACAA1 and SOCS2; or ACAA1 and DCN. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0184] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of an AP1M2 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. Combinations or subcombinations including AP1M2 are AP1M2 and ACAA1; AP1M2 and CGN; AP1M2 and DDR1; AP1M2 and EPS8L2; AP1M2 and FASTKD1; AP1M2 and GMIP; AP1M2 and IKBKE; AP1M2 and P2RX4; AP1M2 and P4HB; AP1M2 and PHKG2; AP1M2 and PPFIBP2; AP1M2 and PPP1R16A; AP1M2 and RASSF7; AP1M2 and RNF183; AP1M2 and SIRT6; AP1M2 and TJP3; AP1M2 and EFEMP2; AP1M2 and SOCS2; or AP1M2 and DCN. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0185] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a CGN biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. Combinations or subcombinations including CGN are CGN and AP1M2; ACAA1 and CGN; CGN and DDR1; CGN and EPS8L2; CGN and FASTKD1; CGN and GMIP; CGN and IKBKE; CGN and P2RX4; CGN and P4HB; CGN and PHKG2; CGN and PPFIBP2; CGN and PPP1R16A; CGN and RASSF7; CGN and RNF183; CGN and SIRT6; CGN and TJP3; CGN and EFEMP2; CGN and SOCS2; or CGN and DCN. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0186] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a DDR1 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. A preferred combination or subcombination useful for detecting endometrial cancer or an increased likelihood of endometrial cancer is DDR1 and P4HB; DDR1 and GMIP; DDR1 and IKBKE; DDR1 and EFEMP2; DDR1 and SOCS2; DDR1, P4HB, and GMIP; DDR1, P4HB, GMIP, and IKBKE; DDR1, P4HB, GMIP, IKBKE and EFEMP2; or DDR1, GMIP, IKBKE, P4HB, and SOCS2. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0187] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of an EPS8L2 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. Combinations or subcombinations including EPS8L2 are EPS8L2 and AP1M2; EPS8L2 and CGN; EPS8L2 and DDR1; EPS8L2 and EPS8L2; EPS8L2 and FASTKD1; EPS8L2 and GMIP; EPS8L2 and IKBKE; EPS8L2 and P2RX4; EPS8L2 and P4HB; EPS8L2 and PHKG2; EPS8L2 and PPFIBP2; EPS8L2 and PPP1R16A; EPS8L2 and RASSF7; EPS8L2 and RNF183; EPS8L2 and SIRT6; EPS8L2 and TJP3; EPS8L2 and EFEMP2; EPS8L2 and SOCS2; EPS8L2 and ACAA1; or EPS8L2 and DCN. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0188] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a FASTKD1 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. A preferred combination or subcombination useful for detecting endometrial cancer or an increased likelihood of endometrial cancer is FASTD1 and P4HB; FASTKD1 and GMIP; FASTKD1 and IKBKE; FASTKD1 and EFEMP2; FASTKD1 and SOCS2; FASTD1 and DDR1; FASTKD1 and SIRT6; FASTKD1 and PHKG2; FASTKD1, P4HB, and GMIP; FASTKD1, P4HB and IKBKE; FASTKD1, P4HB, and EFEMP2; FASTKD1, P4HB, EFEMP2, IKBKE, and GMIP; FASTKD1, P4HB, EFEMP2, SIRT6, DDR1, and GMIP; or FASTKD1, P4HB, EFEMP2, SIRT6, PHKG2, and GMIP. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0189] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a GMIP biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. A preferred combination or subcombination useful for detecting endometrial cancer or an increased likelihood of endometrial cancer is GMIP and P4HB; FASTKD1 and GMIP; GMIP and IKBKE; GMIP and EFEMP2; GMIP and SOCS2; GMIP and DDR1; GMIP and SIRT6; GMIP and PHKG2; GMIP, P4HB, and IKBKE; GMIP, SOCS2, and IKBKE; GMIP, SOCS2, and P4HB; GMIP, IKBKE, P4HB, and EFEMP2; GMIP, IKBKE, P4HB, and SOCS2; GMIP, P4HB, EFEMP2, IKBKE, and FASTKD1; GMIP, P4HB, EFEMP2, SIRT6, DDR1, and FASTKD1; or GMIP, P4HB, EFEMP2, SIRT6, PHKG2, and FASTKD1. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0190] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of an IKBKE biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. A preferred combination or subcombination useful for detecting endometrial cancer or an increased likelihood of endometrial cancer is IKBKE and P4HB; IKBKE and GMIP; IKBKE and FASTKD1; IKBKE and EFEMP2; IKBKE and SOCS2; IKBKE and DDR1; IKBKE and SIRT6; IKBKE and PHKG2; IKBKE, P4HB, and GMIP; IKBKE, P4HB, and EFEMP2; IKBKE, GMIP, and EFEMP2; IKBKE, P4HB, and SOCS2; IKBKE, GMIP, P4HB, and SOCS2; IKBKE, GMIP, P4HB, and EFEMP2; IKBKE, P4HB, EFEMP2, GMIP, and FASTKD1; or IKBKE, DDR1, GMIP, P4HB, PHKG2, SIRT6, and EFEMP2. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0191] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a P2RX4 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. Combinations or subcombinations including P2RX4 are P2RX4 and AP1M2; P2RX4 and CGN; P2RX4 and DDR1; P2RX4 and EPS8L2; P2RX4 and FASTKD1; P2RX4 and GMIP; P2RX4 and IKBKE; P2RX4 and P4HB; P2RX4 and PHKG2; P2RX4 and PPFIBP2; P2RX4 and PPP1R16A; P2RX4 and RASSF7; P2RX4 and RNF183; P2RX4 and SIRT6; P2RX4 and TJP3; P2RX4 and EFEMP2; P2RX4 and SOCS2; P2RX4 and ACAA1; or P2RX4 and DCN. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0192] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a P4HB biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. A preferred combination or subcombination useful for detecting endometrial cancer or an increased likelihood of endometrial cancer is FASTD1 and P4HB; P4HB and GMIP; P4HB and IKBKE; P4HB and EFEMP2; P4HB and SOCS2; P4HB and DDR1; P4HB and SIRT6; P4HB and PHKG2; P4HB, GMIP, and IKBKE; P4HB, GMIP, and SOCS2; P4HB, GMIP, and EFEMP2; P4HB, IKBKE, GMIP, and SOCS2; P4HB, IKBKE, GMIP, and EFEMP2; P4HB, EFEMP2, IKBKE, GMIP, and FASTKD1; P4HB, EFEMP2, SIRT6, GMIP, DDR1, and FASTKD1; P4HB, EFEMP2, SIRT6, GMIP, PHKG2, and FASTKD1; or DDR1, FASTKD1, GMIP, IKBKE, P4HB, PHKG2, SIRT6, and EFEMP2. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0193] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a PHKG2 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. A preferred combination or subcombination useful for detecting endometrial cancer or an increased likelihood of endometrial cancer is PHKG2 and P4HB; PHKG2 and GMIP; PHKG2 and IKBKE; PHKG2 and EFEMP2; PHKG2 and SOCS2; PHKG2 and DDR1; PHKG2 and SIRT6; FASTKD1 and PHKG2; PHKG2, P4HB, and EFEMP2; PHKG2, P4HB, GMIP; PHKG2, P4HB, IKBKE, and EFEMP2; PHKG2, P4HB, IKBKE, and SOCS2; P4HB, EFEMP2, SIRT6, GMIP, PHKG2, and FASTKD1; or DDR1, FASTKD1, GMIP, IKBKE, P4HB, PHKG2, SIRT6, and EFEMP2 In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0194] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a PPFIBP2 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. Combinations or subcombinations including PPFIBP2 are PPFIBP2 and AP1M2; PPFIBP2 and CGN; PPFIBP2 and DDR1; PPFIBP2 and EPS8L2; PPFIBP2 and FASTKD1; PPFIBP2 and GMIP; PPFIBP2 and IKBKE; PPFIBP2 and P2RX4; PPFIBP2 and P4HB; PPFIBP2 and PHKG2; PPFIBP2 and PPP1R16A; PPFIBP2 and RASSF7; PPFIBP2 and RNF183; PPFIBP2 and SIRT6; PPFIBP2 and TJP3; PPFIBP2 and EFEMP2; PPFIBP2 and SOCS2; PPFIBP2 and ACAA1; or PPFIBP2 and DCN. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0195] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a PPP1R16A biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. Combinations or subcombinations including PPP1R16A are PPP1R16A and AP1M2; PPP1R16A and CGN; PPP1R16A and DDR1; PPP1R16A and EPS8L2; PPP1R16A and FASTKD1; PPP1R16A and GMIP; PPP1R16A and IKBKE; PPP1R16A and P2RX4; PPP1R16A and P4HB; PPP1R16A and PHKG2; PPFIBP2 and PPP1R16A; PPP1R16A and RASSF7; PPP1R16A and RNF183; PPP1R16A and SIRT6; PPP1R16A and TJP3; PPP1R16A and EFEMP2; PPP1R16A and SOCS2; PPP1R16A and ACAA1; or PPP1R16A and DCN. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0196] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a RASSF7 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. Combinations or subcombinations including RASSF7 are RASSF7 and AP1M2; RASSF7 and CGN; RASSF7 and DDR1; RASSF7 and EPS8L2; RASSF7 and FASTKD1; RASSF7 and GMIP; RASSF7 and IKBKE; RASSF7 and P2RX4; RASSF7 and P4HB; RASSF7 and PHKG2; RASSF7 and PPP1R16A; RASSF7 and RNF183; RASSF7 and SIRT6; RASSF7 and TJP3; RASSF7 and EFEMP2; RASSF7 and SOCS2; RASSF7 and ACAA1; or RASSF7 and DCN. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0197] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a RNF183 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. Combinations or subcombinations including RNF183 are RNF183 and AP1M2; RNF183 and CGN; RNF183 and DDR1; RNF183 and EPS8L2; RNF183 and FASTKD1; RNF183 and GMIP; RNF183 and IKBKE; RNF183 and P2RX4; RNF183 and P4HB; RNF183 and PHKG2; RNF183 and PPP1R16A; RASSF7 and RNF183; RNF183 and SIRT6; RNF183 and TJP3; RNF183 and EFEMP2; RNF183 and SOCS2; RNF183 and ACAA1; or RNF183 and DCN. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0198] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a SIRT6 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. A preferred combination or subcombination useful for detecting endometrial cancer or an increased likelihood of endometrial cancer is SIRT6 and P4HB; SIRT6 and GMIP; SIRT6 and IKBKE; SIRT6 and EFEMP2; SIRT6 and SOCS2; SIRT6 and DDR1; FASTKD1 and SIRT6; SIRT6 and PHKG2; SIRT6, P4HB, and EFEMP2; SIRT6, P4HB, and IKBKE; SIRT6, IKBKE, and EFEMP2; SIRT6, P4HB, and SOCS2; SIRT6, P4HB, IKBKE, and GMIP; SIRT6, P4HB, EFEMP2, GMIP, DDR1, and FASTKD1; SIRT6, P4HB, EFEMP2, GMIP, PHKG2, and FASTKD1; or SIRT6, P4HB, EFEMP2, GMIP, IKBKE, PHKG2, DDR1, and FASTKD1. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0199] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a TJP3 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, EFEMP2, SOCS2, and DCN. Combinations or subcombinations including TJP3 are TJP3 and AP1M2; TJP3 and CGN; TJP3 and DDR1; TJP3 and EPS8L2; TJP3 and FASTKD1; TJP3 and GMIP; TJP3 and IKBKE; TJP3 and P2RX4; TJP3 and P4HB; TJP3 and PHKG2; TJP3 and PPP1R16A; TJP3 and RNF183; TJP3 and SIRT6; TJP3 and RASSF7; TJP3 and EFEMP2; TJP3 and SOCS2; TJP3 and ACAA1; or TJP3 and DCN. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0200] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of an EFEMP2 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, SOCS2, and DCN. A preferred combination or subcombination useful for detecting endometrial cancer or an increased likelihood of endometrial cancer is EFEMP2 and P4HB; EFEMP2 and GMIP; EFEMP2 and IKBKE; FASTKD1 and EFEMP2; EFEMP2 and SOCS2; EFEMP2 and DDR1; EFEMP2 and SIRT6; EFEMP2 and PHKG2; EFEMP2, P4HB, and IKBKE; EFEMP2, IKBKE, and GMIP; EFEMP2, IKBKE, and FASTKD1; EFEMP2, GMIP, and DDR1; EFEMP2, SIRT6, and FASTKD1; EFEMP2, IKBKE, GMIP, and P4HB; EFEMP2, P4HB, IKBKE, GMIP, and FASTKD1; EFEMP2, P4HB, SIRT6, DDR1, GMIP, and FASTKD1; EFEMP2, P4HB, SIRT6, PHKG2, GMIP, and FASTKD1; or EFEMP2, P4HB, IKBKE, GMIP, DDR1, PHKG2, SIRT6, and FASTKD1; In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0201] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a SOCS2 biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, and DCN. A preferred combination or subcombination useful for detecting endometrial cancer or an increased likelihood of endometrial cancer is SOCS2 and P4HB; SOCS2 and GMIP; SOCS2 and IKBKE; SOCS2 and EFEMP2; FASTKD1 and SOCS2; SOCS2 and DDR1; SOCS2 and SIRT6; SOCS21 and PHKG2; SOCS2, P4HB, and IKBKE; SOCS2, GMIP, and P4HB; SOCS2, P4HB, and IKBKE; GMIP, P4HB, IKBKE, and SOCS2; SOCS2, GMIP, IKBKE, P4HB, and DDR1; or SOCS2, DDR1, FASTKD1, GMIP, IKBKE, P4HB, PHKG2, SIRT6, and EFEMP2. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0202] In one embodiment, the invention provides a method for diagnosing endometrial cancer comprising determining the level of a DCN biomarker in combination with the level of one or more biomarkers. In a specific aspect of this embodiment the one or more biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classify endometrial cancer and auxiliary biomarkers for detecting endometrial cancer. In one aspect of this embodiment, the one or more biomarkers are chosen from differential diagnosis biomarkers, biomarkers useful for detecting endometrial cancer, and biomarkers useful for classifying endometrial cancer. In one aspect of this embodiment, the one or more biomarkers useful for detecting endometrial cancer are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, and SOCS2. Combinations or subcombinations including DCN are DCN and AP1M2; DCN and CGN; DCN and DDR1; DCN and EPS8L2; DCN and FASTKD1; DCN and GMIP; DCN and IKBKE; DCN and P2RX4; DCN and P4HB; DCN and PHKG2; DCN and PPP1R16A; DCN and RNF183; DCN and SIRT6; DCN and RASSF7; DCN and EFEMP2; DCN and SOCS2; or DCN and ACAA1. In one aspect of this embodiment, the level(s) of gene expression of the biomarker is determined. In another aspect of this embodiment, the level(s) of protein expression is determined. In one aspect of this embodiment, a tumor or suspected sample is analyzed. In another aspect a fluid sample is analyzed. In another aspect of this embodiment, a sample obtained from uterine fluid is analyzed. In yet another aspect of this embodiment, a serum or blood samples is analyzed. In one aspect, the sample that is analyzed is obtained from a cell.

[0203] In a preferred aspect of the in vitro diagnostic method of the invention the levels of a combination of markers is detected where said combination comprises IKBKE and P4HB; IKBKE and SOCS2; P4HB and SOCS2; GMIP and IKBKE; GMIP and P4HB; GMIP and SOCS2; GMIP, SOCS2, and IKBKE; GMIP, SOCS2, and P4HB; GMIP, IKBKE, and P4HB; IKBKE, P4HB, and SOCS2; GMIP, IKBKE, P4HB, and SOCS2; GMIP, SOCS2, IKBKE, and EPS8L2; GMIP, SOCS2, P4HB, and EPS8L2; GMIP, IKBKE, P4HB, and EPS8L2; IKBKE, P4HB, SOCS2, and EPS8L2; GMIP, IKBKE, P4HB, SOCS2, and DDR1; GMIP, IKBKE, P4HB, SOCS2, EPS8L2, and PPP1R16A; GMIP, IKBKE, P4HB, SOCS2, PHKG2, and RASSF7; GMIP, IKBKE, P4HB, SOCS2, EPS8L2, and DDR1; GMIP, IKBKE, P4HB, SOCS2, EPS8L2, PPP1R16A, and DDR1; DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, RASSF7, SIRT6, TJP3, and SOCS2; or DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, RASSF7, SIRT6, TJP3, RNF183 and SOCS2.

[0204] In another preferred aspect of the in vitro diagnostic method of the invention a the levels of a combination of markers is detected where said combination comprises GMIP, IKBKE, P4HB, SOCS2 and FASTKD1; GMIP, IKBKE, P4HB, SOCS2 and DDR1; GMIP, IKBKE, P4HB, SOCS2 and PHKG2; GMIP, IKBKE, P4HB, SOCS2 and SIRT6; GMIP, IKBKE, P4HB, SOCS2 and ACAA1; GMIP, IKBKE, P4HB, SOCS2 and EFEMP2; GMIP, IKBKE, P4HB, SOCS2 and EPS8L2; GMIP, IKBKE, P4HB, SOCS2 and P2RX4; GMIP, IKBKE, P4HB, SOCS2 and PPFIBP2; GMIP, IKBKE, P4HB, SOCS2 and PPP1R16A; GMIP, IKBKE, P4HB, SOCS2, ACAA1 and FASTKD1; GMIP, IKBKE, P4HB, SOCS2, PHKG2 and FASTKD1; GMIP, IKBKE, P4HB, SOCS2, SIRT6 and FASTKD1; ACAA1, AP1M2, EPS8L2, IKBKE, P2RX4, P4HB, PPFIBP2, PPP1R16A, SIRT6, and EFEMP2; GMIP, IKBKE, P4HB, and EFEMP2; DDR1, FASTKD1, PHKG2, SIRT6, SOCS2, GMIP, IKBKE, P4HB, and EFEMP2; DDR1, FASTKD1, PHKG2, SIRT6, GMIP, IKBKE, P4HB, and EFEMP2; or P4HB, EFEMP2, IKBKE, GMIP, and FASTKD1.

[0205] In yet another preferred aspect of the in vitro diagnostic method of the invention the levels of a combination of markers is detected where said combination comprises GMIP, IKBKE, P4HB, EFEMP2 and FASTKD1; GMIP, IKBKE, P4HB, EFEMP2 and DDR1; GMIP, IKBKE, P4HB, EFEMP2 and PHKG2; GMIP, IKBKE, P4HB, EFEMP2 and SIRT6; GMIP, IKBKE, P4HB, EFEMP2 and ACAA1; GMIP, IKBKE, P4HB, SOCS2 and EFEMP2; GMIP, IKBKE, P4HB, EFEMP2 and EPS8L2; GMIP, IKBKE, P4HB, EFEMP2 and P2RX4; GMIP, IKBKE, P4HB, EFEMP2 and PPFIBP2; GMIP, IKBKE, P4HB, EFEMP2 and PPP1R16A; GMIP, IKBKE, P4HB, EFEMP2, ACAA1 and FASTKD1; GMIP, IKBKE, P4HB, EFEMP2, PHKG2 and FASTKD1; or GMIP, IKBKE, P4HB, EFEMP2, SIRT6 and FASTKD1.

[0206] Auxiliary Biomarkers

[0207] "Auxiliary biomarkers" refer to biomarkers that can be used in conjunction with the one or more biomarkers of Table 1. The auxiliary biomarkers can be used in the methods of the invention to provide further characterization of a disease or condition a patient may have.

[0208] Differential diagnosis biomarkers are useful for distinguishing between diseases that may present with similar clinical symptoms. For example, a patient may have symptoms of endometrial cancer (e.g., vaginal bleeding and/or pelvic pain) but these symptoms can also be caused by different diseases (e.g., ovarian cancer). Therefore, the differential diagnosis biomarkers provide information for characterization a disease. Examples of diseases that may present similar symptoms as endometrial cancer include uterine fibroids, endometriosis, endometrial hyperplasia, uterine sarcoma--another type of uterus cancer, uterine leiomyomas, endometrial polyp (type of polyp), cervical cancer, atrophic endometrium, adenomyosis, atrophic vaginitis, ovarian tumour, leiomyosarcoma, and endometrial proliferation.

[0209] According to the inventors' finding that the level of biomarkers in primary endometrial cancer tissue can be correlated to their levels in uterine fluid, it is contemplated that uterine fluid samples can be used for differential diagnosis of conditions other than endometrial cancer. Thus, in one aspect, the invention provides a method for the differential diagnosis of endometrial cancer by obtaining a uterine fluid sample from a patient and determining the level of one or more biomarkers that are capable of distinguishing endometrial cancer from non-endometrial cancer. Differential diagnosis biomarkers for endometriosis are useful for distinguishing endometriosis from endometrial cancer. Differential diagnosis biomarkers for ovarian cancer are useful for distinguishing ovarian cancer from endometrial cancer. Examples of biomarkers useful for distinguishing endometrial cancer from ovarian cancer include, but are not limited to, those described in Yurkovetsky et al. (Gyn. Onc. (2007) 107:58-65) where they reported a five-biomarker panel of prolactin, GH, eotaxin, E-selectin, and TSH for discriminating endometrial cancer from ovarian and breast cancer.

[0210] A number of endometrial cancer biomarkers have been identified. CA 125 correlates with tumor size and stage and is an independent predictor of the extrauterine spread. Serum markers for the detection of uterine cancer have been reported in the literature.

[0211] Prognosis biomarkers: Elevated levels of CA 125, CA 15-3, and CA 19-9 are associated with shorter survival time. They found serum CA 125 CA 15-3 and CEA are higher in patients with Stage III disease as compared to stage I. Another group of prognostic markers include estrogen receptor, progesterone receptor, and HER2.

[0212] Biomarkers for classifying endometrial cancer include those for estimating stage of the cancer, cell-type, and/or type of endometrial cancer (e.g., type I verus type II). Examples of biomarkers for classifying endometrial cancer include, but are not limited to, those described in Sugiyama et al. (2003) Clin. Can. Res. 9:5589-5600. Genes showing higher expression in type I as compared to type II include MMP11, RHOG, and platelet-derived growth factor B subunit precursor, STAT2, octamer-binding transcription factor 1, and GATA-6, growth factor VEGF-C precursor, caspase (caspase 1/IL-1 .beta. converting enzyme). Genes showing higher expression in type II as compared to type I included PIRIN, EGR1, STAT1, IFN regulatory factor 1, and KRAS. Konecny et al. ((2009) British Journal of Cancer 100, 89-95) report that the rate HER2 gene amplification as measured by fluorescence in situ hybridization was greater in type II cancers whereas EGFR expression as measured by IHC techniques was significantly lower in type II cancers. Deng et al. ((2005) Clin. Can. Res. vol. 11, no 23:8258-8264) report that EIG121 is a marker for type I estrogen associated cancers. Markers for classifying endometrial cancer can also be used to distinguish different histological types of endometrial cancer like serous and endometrioid cancers. Risinger et al. ((2003) Canc. Res. 63:6-11) identified biomarkers that could distinguish papillary serous cancers from endometrioid cancers. For example AGR2, TFF3, DUSP6, IGF2, FOLR1, and UCHL1 were found to be differentially expressed between papillary serous and endometrioid cancers as found by microarray and validated by RT-PCR. AGR2, TFF3, DUSP6 were found to be upregulated in endometrioid type cancers whereas IGF2, FOLR1 and UCHL1 were found to be upregulated in papillary serous cancers.

[0213] According to the inventor's finding that the level of biomarkers in primary endometrial cancer tissue can be correlated to their levels in uterine fluid, it is contemplated that uterine fluid samples can be used to classify the type of endometrial cancer. Classifying the type of endometrial cancer can refer to distinguishing type I and type II cancers. Classifying the type of endometrial cancer can also refer to determining the histological type and/or sub-type of endometrial cancer. Thus, in one aspect, the invention provides a method for classifying an endometrial cancer by obtaining a uterine fluid sample from a patient and determining the level of one or more biomarkers that are capable of classifying an endometrial cancer.

[0214] "Auxiliary biomarkers for detecting endometrial cancer" refer to biomarkers that can be used in addition to the biomarkers of Table 1 for the diagnosis of endometrial cancer and/or an increased risk of having endometrial cancer: Yurkovetsky et al. (Gyn. Onc. (2007) 107:58-65) identified that prolactin is a serum biomarker with sensitivity and specificity for endometrial cancer. Yurkovetsky et al. found that prolactin, GH, eotaxin, E-selectin, and TSH were useful markers for diagnosising endometrial cancer.

[0215] In some aspects of these embodiments, one or more auxiliary biomarkers are examined for alterations in a sample from a patient suspected of having endometrial cancer. In a specific aspect, the auxiliary biomarkers are chosen from serum biomarkers. In a more specific aspect the serum biomarkers are one or more proteins chosen from CA 125, CA 15-3, CA 19-9, CEA, AFP, CA 72-4, VEGF, bFGF, IGFBPI, HGF, ErbB2, EGFR, TGF .alpha., Fas, FasL, Cyfra 21-1, MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, tPAI, sICAM, sVCAM, sE-selectin, adiponectin, resistin, IL-6, IL-8, TNF .alpha., TNFR I, G-CSF, CD40L, IL-2R, IP-10, MCP-1, MIP-1.alpha., MIP-1.beta., MIF, eotaxin, RANTES, FSH, LH, TSH, ACTH, Prolactin, GH, .beta.HCG, hK8, hK10, active PAI-1, ULBP-1, ULBP-2, ULBP-3, MICA, angiostatin, SCC, serum amyloid A, TTR, 5100, mesothelin, and myeloperoxidase (MPO). In a more specific aspect, the serum biomarkers are chosen from prolactin, GH, eotaxin, e-selectin and FSH. In an even more specific aspect, the serum biomarker is prolactin. In some aspects, the auxiliary biomarker(s) can be examined in uterine aspirates (e.g., mRNA level and/or protein levels).

[0216] Samples

[0217] The invention, in some embodiments, relates to characterizing one or more biomarkers of Table 1, from a sample from a patient suspected of having endometrial cancer or desiring screening for cancer. Examples of such samples that can be used in the invention are fluid, tissue samples, and/or cells. Depending on the specific marker, the methods used for characterizing the biomarkers of the invention can include e.g., examining the DNA copy number of the gene corresponding to the biomarker, detecting the protein related to the biomarker, determining the mRNA expression levels of the biomarker, etc. The invention is useful for a number of applications including diagnosis, prognosis, staging, predicting response to therapy. The inventors have found evidence of differential expression of the biomarkers of Table 1 in a number of different samples including mRNA in primary tumor, protein in primary tumor, and mRNA in aspirates, and protein in aspirates. The biomarkers of Table 1 include those that are overexpressed in samples from endometrial cancer patients as compared to normal levels. Additionally some of the biomarkers of Table 1 are underexpressed in samples from endometrial cancer patients as compared to normal levels

[0218] The invention, in some embodiments, relates to characterizing one or more of the biomarkers of Table 1, from a patient sample (e.g., tumor, cancer cell, sample suspected of being cancer, body fluid (e.g., uterine fluid), blood, serum, plasma, and vaginal blood/discharge) and/or from a "normal" cell, from an individual (or alternatively a control value can be used in lieu of the normal value from the cell).

[0219] In one aspect, the sample to be analyzed is obtained from a patient that has risk factors for endometrial cancer. Risk factors for endometrial cancer include, but are not limited to, having Lynch Syndrome, being genetically related to a person having Lynch Syndrome, obese, taking estrogen-alone hormone replacement therapy, and prior treatment with tamixofen.

[0220] In one aspect of this embodiment, the sample is analyzed is a uterine fluid sample. In one aspect, the sample is that is used is obtained by using a soft, straw-like device (pipelle) to suction off a small sample of lining from the uterus. In one aspect, the sample is obtained by using a sharp-edged tool called a curette by scraping a small sample and collect it with a syringe or suction (e.g., dilation and curettage). In one aspect, the sample is obtained by using an electronic suction device (e.g., Vabra aspiration). In one aspect, the sample is obtained by using a spray of liquid (jet irrigation) to wash off some of the tissue that lines the uterus. In some aspects, a brush may be used to remove some of the lining before the washing is done.

[0221] In one embodiment, the sample for analyzing the biomarkers is obtained using a syringe or pipelle type device. In one embodiment, the device for collection of the uterine fluid sample from an internal cavity (e.g., uterus) of a patient, comprises a barrel having an opening at one end thereof, a plunger operable axially within the barrel, the barrel and the plunger defining a fluid chamber having a volume which varies on axial movement of the plunger within the barrel, and a hollow, elongate tube extending from the fluid chamber through the opening in the barrel, the tube being in operative engagement with the plunger for axial movement to extend and retract the tube within respect to the barrel on axial movement of the plunger, and the tube being in fluid communication with the fluid chamber to provide a fluid flow path to and from the fluid chamber through the hollow tube. In one aspect of this embodiment, after the sample is obtained using the device, it is stored in an agent that preserves the integrity of the biomarkers of interest. For example, when the biomarker being analyzed is a nucleic acid like RNA, the sample can be stored in an agent that prevents degradation of RNA molecules in the sample, or if the biomarker is a protein the sample can be stored e.g., in an agent that preserves protein. Example of agents that prevent degradation of RNA molecules in a sample are RNase inhibitors (e.g., RNEASY.TM. from Qiagen, SUPERase.cndot.In.TM. from Ambion or ScriptGuard.TM. RNase Inhibitor from epicenter biotechnologies) or molecules that precipitate RNA out of biological solutions (e.g., triphenylmethane dyes (e.g., methyl green, crystal violet, and pararosaniline), cresyl violet, polyamines, and cobalt ions). Example of agents that prevent the degradation of protein is protease inhibitors (e.g., PMSF (phenylmethanesulfonyl fluoride, Complete protease inhibitor cocktail from Roche, or Pepstatin) or agents that fix tissues (formalin).

[0222] Thus the invention provides in one embodiment, an in vitro diagnostic method for endometrial cancer comprising obtaining a uterine fluid aspirate sample from a patient having a symptom or risk factor for endometrial cancer and determining the level of from 1 to 100 biomarkers markers that are differentially expressed in endometrial cancer as compared to control values representative of individuals not affected by endometrial cancer, wherein (1) if the levels of 1-100 biomarkers are upregulated in the endometrial aspirate sample in the patient and in the control value then the patient has an increased likelihood of having endometrial cancer and wherein (2) if the level of the 1-100 biomarkers are downregulated in the aspirate sample and then the patient has an increased likelihood of having endometrial cancer. The biomarkers of this aspect can be any biomarkers that are differentially represented in endometrial cancer patient samples compared to samples from patients not affected with endometrial cancer and are useful for diagnosis of endometrial cancer or an increased likelihood of endometrial cancer. Preferred biomarkers are the 1-20 described herein in Table 1.

[0223] Methods of Detecting Biomarkers

[0224] The invention relates to the identification of biomarkers that are useful for diagnosing endometrial cancer. The invention provides methods for detecting one or more of the biomarkers of Table 1 for diagnosing endometrial cancer. The method of the invention can be used to detect one or more proteins corresponding to the biomarkers of Table 1 for diagnosing endometrial cancer. The method of the invention can be used to detect one or more mRNA corresponding to the biomarkers of Table 1 for diagnosing endometrial cancer. The biomarkers can be detected in a sample obtained from a patient e.g., a sample obtained from uterine tissue, uterine fluid, or blood.

[0225] In some embodiments, the method of the invention involves obtaining a sample and determining the level of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, of the biomarkers of Table 1 in the sample. In a specific aspect, the method involves determining the level of 2 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 3 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 4 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 5 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 6 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 7 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 8 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 9 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 10 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 11 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 12 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 13 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 14 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 15 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of 20 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of from 2 to 20 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of from 3 to 20 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of from 3 to 17 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of from 4 to 17 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of from 5 to 17 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of from 10 to 17 of the biomarkers listed in Table 1. In one aspect of this embodiment, the method involves determining the level of less than 500 different biomarkers. In one aspect of this embodiment, the method involves determining the level of less than 250 different biomarkers. In one aspect of this embodiment, the method involves determining the level of less than 100 different biomarkers. In one aspect of this embodiment, the method involves determining the level of less than 50 different biomarkers. Increased levels of one or more biomarkers of Table 1 that are overexpressed and/or decreased eels of one or more biomarkers of Table 1 that are underexpressed indicate that there is an increased likelihood of endometrial cancer.

[0226] It is understood that in some aspects of this embodiment, the biomarkers analyzed include more than those listed in Table 1.

[0227] In some aspects of these embodiments, the method involves obtaining a sample and determining the level of mRNA of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, of the biomarkers of Table 1 in the sample. In a specific aspect, the method involves determining the level of mRNA of 2 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 3 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 4 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 5 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 6 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 7 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 8 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 9 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 10 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 11 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 12 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 13 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 14 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 15 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of 20 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of from 2 to 20 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of from 3 to 20 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of from 3 to 17 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of from 4 to 17 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of from 5 to 17 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the level of mRNA of from 10 to 20 of the biomarkers listed in Table 1. In one aspect of this embodiment, the method involves determining the level of mRNA of less than 500 different biomarkers. In one aspect of this embodiment, the method involves determining the level of mRNA of less than 250 different biomarkers. In one aspect of this embodiment, the method involves determining the level of mRNA of less than 100 different biomarkers. In one aspect of this embodiment, the method involves determining the level of mRNA of less than 50 different biomarkers. Increased levels of one or more mRNAs corresponding to the biomarkers of Table 1 that are overexpressed and/or decreased levels of one or more biomarkers of Table 1 that are underexpressed indicate that there is an increased likelihood of endometrial cancer. It is understood that in some aspects of this embodiment, the biomarkers analyzed include more than those listed in Table 1.

[0228] In some aspects of these embodiments, the method involves obtaining a sample and determining the protein level of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, of the biomarkers of Table 1 in the sample. In a specific aspect, the method involves determining the protein level of 2 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 3 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 4 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 5 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 6 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 7 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 8 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 9 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 10 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 11 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 12 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 13 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 14 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 15 or more biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of 20 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of from 2 to 20 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of from 3 to 20 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of from 3 to 17 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of from 4 to 17 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of from 5 to 17 of the biomarkers listed in Table 1. In a specific aspect, the method involves determining the protein level of from 10 to 17 of the biomarkers listed in Table 1. In one aspect of this embodiment, the method involves determining the protein level of less than 500 different biomarkers. In one aspect of this embodiment, the method involves determining the protein level of less than 250 different biomarkers. In one aspect of this embodiment, the method involves determining the protein level of less than 100 different biomarkers. In one aspect of this embodiment, the method involves determining the protein level of less than 50 different biomarkers. In one aspect of this embodiment, the method involves determining the protein level of from 1 to 10 different biomarkers. Increased levels of one or more proteins corresponding to the biomarkers of Table 1 indicate that there is an increased likelihood of endometrial cancer. It is understood that in some aspects of this embodiment, the biomarkers analyzed include more than those listed in Table 1.

[0229] In one embodiment, the invention provides a method for detecting one or more protein biomarkers in serum, blood, and/or plasma. In a specific aspect of this embodiment, the one or more biomarkers are chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN. In a more specific aspect, the one or more biomarkers are chosen from IKBKE, P4HB, SOCS2, GMIP, DDR1, EPS8L2, PPP1R16A, P2RX4, PHKG2, RASSF7, SIRT6, TJP3, AP1M2, RNF183, and DCN. In another specific aspect of this embodiment, the method comprises detecting the level of IKBKE. In another specific aspect of this embodiment, the method comprises detecting the level of P4HB. In another specific aspect of this embodiment, the method comprises detecting the level of SOCS2. In another specific aspect of this embodiment, the method comprises detecting the level of GMIP. In another specific aspect of this embodiment, the method comprises detecting the level of AP1M2. In another specific aspect of this embodiment, the method comprises detecting the level of EPS8L2. In another specific aspect of this embodiment, the method comprises detecting the level of DDR1. In another specific aspect of this embodiment, the method comprises detecting the level of CGN. In another specific aspect of this embodiment, the method comprises detecting the level of TJP3.

[0230] In some aspects of these embodiments, the method involves determining the level of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, or 50 or more of biomarkers in addition to one or more of those listed in Table 1. These markers can be those whose expression levels are known to be altered in patients having endometrial cancer. Alternatively, the additional biomarkers can be used for differential diagnosis of other diseases (e.g., endometriosis, ovarian cancer, and fibroids), for classifying the type of cancer, prognostic information and/or for providing information for selecting a therapy. In a specific aspect of this embodiment, the additional biomarkers are analyzed in uterine fluid samples.

[0231] In a specific aspect of the invention, the one or more biomarkers listed in Table 1 are detected on an array having different probes on the array which are oligonucleotides having from about 5 to 200 bases in length. In another specific aspect, each of the different probes on the array is an oligonucleotide having from about 15 to 200, 15 to 150, 15 to 100, 15 to 75, 15 to 60, or 20 to 55 bases in length. In one aspect, the array has probes to 2 or more biomarkers listed in Table 1. In one aspect, the array has probes to 3 or more biomarkers listed in Table 1. In one aspect, the array has probes to 4 or more biomarkers listed in Table 1. In one aspect, the array has probes to 5 or more biomarkers listed in Table 1. In one aspect, the array has probes to 6 or more biomarkers listed in Table 1. In one aspect, the array has probes to 7 or more biomarkers listed in Table 1. In one aspect, the array has probes to less than 1000 different genes. In one aspect, the array has probes to less than 500 different genes. In one aspect, the array has probes to less than 100 different genes.

[0232] In some aspects of these embodiments, the copy number of the one or more biomarkers listed in Table 1 is determined. In another aspect of this embodiment, the copy number profile of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 of the biomarkers of Table 1 (or loci corresponding to the biomarker) are determined for detecting endometrial cancer.

[0233] In one aspect, the invention provides primers that can hybridize to a nucleic acid corresponding to a biomarker listed in Table 1 and be used to amplify a nucleic acid or fragment thereof corresponding to said biomarker for diagnosing endometrial cancer according to the methods of the invention. In a more specific aspect, the primers are designed to amplify one or more exons of the biomarker. In another aspect, the primers are designed to amplify a fragment of one or more exons of the biomarker. In one aspect, the primers are suitable for RT-PCR analysis. In one aspect, the method of the invention involves the use of primers to amplify a nucleic acid corresponding to a biomarker of Table 1, and detecting the amplification product with a probe to the amplification product. In another aspect, the method of the invention involves the use of primers to amplify a nucleic acid corresponding to a biomarker of Table 1, and detecting the amplification product with a dye that allows for quantification of the amplification product.

[0234] In one aspect, the invention provides probes to the biomarkers of Table 1 for detecting a nucleic acid or fragment thereof corresponding to the biomarker. The probes can be used in the methods of the invention e.g., for diagnosing endometrial cancer. In a specific aspect, the probe is for the biomarker mRNA or a nucleic acid, is obtained from the mRNA corresponding to the biomarker. In a specific aspect, the probe corresponds to two contiguous exons of the biomarker of Table 1, (or fragments of two or more contiguous exons). In a specific aspect, the probe corresponds to an exon of the biomarker or a fragment thereof. In a specific aspect, the probe corresponds to at least a portion of the promoter region of the biomarker and at least a portion of exon 1 of the biomarker.

[0235] In one aspect of the invention, a multiplex PCR assay is used to assess the levels of from 2 to 20 of the biomarkers of Table 1 to detect the presence or absence of endometrial cancer. In a more specific aspect, the levels of from 3 to 20 biomarkers of Table 1 are assessed by multiplex PCR. In a more specific aspect, the levels of from 4 to 20 biomarkers of Table 1 are assessed by multiplex PCR. In a more specific aspect, the levels of from 5 to 20 biomarkers of Table 1 are assessed by multiplex PCR. In a more specific aspect, the levels of from 6 to 20 biomarkers of Table 1 are assessed by multiplex PCR. In a more specific aspect, the levels of from 7 to 20 biomarkers of Table 1 are assessed by multiplex PCR. In a more specific aspect, the levels of from 8 to 20 or more biomarkers of Table 1 are assessed by multiplex PCR. In a more specific aspect, the levels of from 9 to 20 biomarkers of Table 1 are assessed by multiplex PCR. In a more specific aspect, the levels of from 10 to 20 or more biomarkers of Table 1 are assessed by multiplex PCR. In a more specific aspect, the levels of from 15 to 20 biomarkers of Table 1 are assessed by multiplex PCR. In a more specific aspect, the levels of from 20 of the biomarkers of Table 1 are assessed by multiplex PCR.

[0236] Quantitative PCR

[0237] In some embodiments, the invention relies on quantitative PCR to determine the level of one or more biomarkers of Table 1. In a specific aspect the quantitative PCR method is quantitative RT-PCR. The methods can be semi-quantitative or fully quantitative.

[0238] The methods of the invention for detecting the biomarkers of the invention can comprise competitive quantitative PCR or real-time quantitative PCR which both estimate target gene concentration in a sample by comparison with standard curves constructed from amplifications of serial dilutions of standard DNA. Quantitative PCR or real-time quantitative PCR differ substantially in how the standard curves are generated. In competitive QPCR, an internal competitor DNA is added at a known concentration to both serially diluted standard samples and unknown (e.g., obtained from a patient) samples. After coamplification, ratios of the internal competitor and target PCR products are calculated for both standard dilutions and unknown samples, and a standard curve is constructed that plots competitor-target PCR product ratios against the initial target DNA concentration of the standard dilutions. Given equal amplification efficiency of competitor and target DNA, the concentration of the latter in patient samples can be extrapolated from this standard curve.

[0239] In real-time QPCR, the accumulation of amplification product is measured continuously in both standard dilutions of target DNA and samples containing unknown amounts of target DNA. A standard curve is constructed by correlating initial template concentration in the standard samples with the number of PCR cycles (C.sub.t) necessary to produce a specific threshold concentration of product. In the test samples, target PCR product accumulation is measured after the same C.sub.t, which allows interpolation of target DNA concentration from the standard curve. Although real-time QPCR permits more rapid and facile measurement of target DNA during routine analyses, competitive QPCR remains an important alternative for target quantification in environmental samples. The coamplification of a known amount of competitor DNA with target DNA is an intuitive way to correct for sample-to-sample variation of amplification efficiency due to the presence of inhibitory substrates and large amounts of background DNA that are obviously absent from the standard dilutions.

[0240] Another type of QPCR is applied quantitatively PCR. Often termed "relative quantitative PCR," this method determines the relative concentrations of specific nucleic acids. In the context of the present invention, RT-PCR is performed on mRNA species isolated from patients. By determining that the concentration of a specific mRNA species, it can be determined if the gene encoding the specific mRNA species is differentially expressed.

[0241] In one embodiment, the invention provides a method comprising, obtaining a test sample from cells, tissue, or fluid of a patient; detecting the level of one or more of the biomarkers of Table 1 and comparing the level of the biomarker(s) in the sample to the level expected for a normal sample (or control value).

[0242] In one embodiment, the invention provides a method comprising, obtaining a suspected tumor sample from a patient; detecting the level of one or more biomarkers listed in Table 1 and comparing the level of biomarker(s) in the sample to the level expected for a normal unaffected sample (or control value).

[0243] In one embodiment, the invention provides a method comprising, obtaining a sample from a patient comprising a cell; detecting the level of one or more of the biomarkers of Table 1 in said cell and comparing the level of the biomarker(s) in the cell to the level expected for a normal unaffected cell (or control value).

[0244] In one embodiment, the invention provides a method comprising, obtaining a test sample from a fluid of a patient; detecting the level of one or more of the biomarkers of Table 1 and comparing the level of the biomarker(s) in the sample to the level expected for a normal unaffected sample. In one aspect of this embodiment, the fluid is uterine fluid obtained by aspiration. In one aspect of this embodiment, the fluid is uterine fluid obtained by aspiration with a CORNIER.TM. pipelle. In one aspect of this embodiment, the fluid is uterine fluid. In another aspect of this embodiment, the fluid is vaginal discharge. In one embodiment, the invention provides a method comprising, obtaining a test sample from a blood or serum sample from a patient; and detecting the level of one or more of the biomarkers of Table 1 and comparing the level of the biomarker(s) in the sample to the level expected for a normal unaffected sample.

[0245] In one embodiment, the invention provides a method comprising, obtaining a test sample from the urine of a patient; detecting the level of one or more of the biomarkers of Table 1 and comparing the level of the biomarkers in the urine to the level expected for a control value.

[0246] In one embodiment, the invention provides a method comprising, obtaining a test sample from the uterus of a patient using a brush; and detecting the level of one or more of the biomarkers of Table 1 and comparing the level of the biomarkers in the sample to the level expected for a normal sample.

[0247] The presence of increased levels of one or more of the biomarkers of Table 1 can indicate endometrial cancer or a precancerous condition in the tissue e.g., endometrial hyperplasia. In one aspect of this embodiment, the method involves identifying a patient in need of analysis of one or more biomarkers of Table 1.

[0248] In another aspect of this embodiment, the present invention provides methods for diagnosing or predicting a endometrial cancer. The method of this aspect can comprise (1) obtaining a test sample from cells, tissue, and/or fluid (2) obtaining a control sample from cells, tissue, or fluid that is normal, or obtaining a normal control value, and (3) detecting or measuring in both the test sample and the control sample the level of one or more mRNA transcripts corresponding to one or more of the biomarkers of Table 1. If the level of the one or more transcripts is higher in the test sample than that in the control sample, this indicates endometrial cancer (and/or and increased risk of having endometrial cancer) or a precancerous condition in the test sample cells or tissue. In another aspect the control sample may be obtained from a different individual or be a normalized value based on baseline data obtained from a population. In one aspect of this embodiment, the method involves identifying a patient in need of analysis of one or more of the biomarkers of Table 1. In one aspect, the patient in need of analysis of one or more of the biomarkers of Table 1 is one that is at risk of having endometrial cancer, is suspected of having endometrial cancer, or and/or is undergoing screening.

[0249] In yet another aspect of this embodiment, the method comprises, obtaining a test sample from cells, tissue, or fluid; detecting the number of DNA copies of one or more of the biomarkers of Table 1 ((e.g., per cell) in the sample; and comparing the number of DNA copies detected (for example, quantitatively and/or qualitatively) in the sample to a control sample or a known value (or a control value), thereby determining whether the copy number of the biomarker(s) is amplified in the test sample. In one aspect of this embodiment, the method involves identifying a patient in need of analysis of one or more of the biomarkers of Table 1. In one aspect, the patient in need of analysis of one or more of the biomarkers of Table 1 is one that is at risk of having endometrial cancer, is suspected of having endometrial cancer, or and/or is undergoing screening.

[0250] In yet another aspect of this embodiment, the method comprises (1) obtaining a test sample from cells, tissue, or fluid; contacting the sample with an antibody to a protein or fragment thereof corresponding to one or more of the biomarkers of Table 1, and detecting in the test sample, the level of the biomarker(s), wherein an increased level the biomarker(s), as compared to a control value indicates the patient may have a precancerous or a cancerous condition. In another aspect, the control value may be obtained from a different individual or be a normalized value based on baseline data obtained from a population. Alternatively, a given level of a biomarker, representative of the endometrial cancer-free population, that has been previously established based on measurements from normal, endometrial cancer-free patients, can be used as a control value. A control data point from a reference database, based on data obtained from control samples representative of an endometrial cancer-free population, also can be used as a control value. In one aspect of this embodiment, the method involves identifying a patient in need of analysis of one or more of the biomarkers of Table 1. In one aspect, the patient in need of analysis of the biomarker(s) is one that is at risk of having endometrial cancer, is suspected of having endometrial cancer, or and/or is undergoing screening.

[0251] In some embodiments, the method of the invention involves comparing the expression of a biomarker of the invention to an endogenous biomarker. For example, the expression level of one or more of the biomarkers listed in Table 1 are normalized to the level of expression of an endogenous biomarker. Thus, in one specific aspect, the endogenous biomarker is chosen from POLR2A, B2M, PFN1, HMBS, G6PD, and PABPN1. The ENSMBL reference numbers are given below for these endogenous biomarkers.

TABLE-US-00003 Name Gene Transcript Protein POLR2A ENSG00000181222 ENST00000322644 ENSP00000314949 B2M ENSG00000166710 ENST00000349264 ENSP00000340858 PFN1 ENSG00000108518 ENST00000225655 ENSP00000225655 HMBS ENSG00000149397 ENST00000278715 ENSP00000278715 G6PD ENSG00000160211 ENST00000393562 ENSP00000377192 PABPN1 ENSG00000100836 ENST00000216727 ENSP00000216727

[0252] Diagnostic and Prognostic Reagents

[0253] The invention provides reagents for detecting the biomarkers of the invention (e.g., those in Table 1). The reagents are useful for detecting protein and nucleic acid levels of the biomarkers of Table 1 for detecting and/or diagnosing endometrial cancer. The reagents below can be used for detecting combinations of the biomarkers to diagnose endometrial cancer. Specific examples of nucleic acids, probes, primers, etc. related to each of the individual biomarkers are given in the Examples.

[0254] In one embodiment, the invention provides an ACAA1 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying an ACAA1 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to an ACAA1 nucleic acid for detecting endometrial cancer.

[0255] In another related aspect, the invention provides an antibody that binds immunologically to an ACAA1 protein for detecting endometrial cancer. In a related aspect the invention provides an ACAA1 polypeptide for generating an antibody. In yet another related aspect, the invention provides an ACAA1 polypeptide for generating an immune response against the marker.

[0256] In one embodiment, the invention provides an AP1M2 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying an AP1M2 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to an AP1M2 nucleic acid for detecting endometrial cancer.

[0257] In another related aspect, the invention provides an antibody that binds immunologically to an AP1M2 protein for detecting endometrial cancer. In a related aspect the invention provides an AP1M2 polypeptide for generating an antibody. In yet another related aspect, the invention provides an AP1M2 polypeptide for generating an immune response against the marker.

[0258] In one embodiment, the invention provides a CGN nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a CGN nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a CGN nucleic acid for detecting endometrial cancer.

[0259] In another related aspect, the invention provides an antibody that binds immunologically to a CGN protein for detecting endometrial cancer. In a related aspect the invention provides a CGN polypeptide for generating an antibody. In yet another related aspect, the invention provides a CGN polypeptide for generating an immune response against the marker.

[0260] In one embodiment, the invention provides a DDR1 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a DDR1 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a DDR1 nucleic acid for detecting endometrial cancer.

[0261] In another related aspect, the invention provides an antibody that binds immunologically to a DDR1 protein for detecting endometrial cancer. In a related aspect the invention provides a DDR1 polypeptide for generating an antibody. In yet another related aspect, the invention provides a DDR1 polypeptide for generating an immune response against the marker.

[0262] In one embodiment, the invention provides an EPS8L2 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying an EPS8L2 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to an EPS8L2 nucleic acid for detecting endometrial cancer.

[0263] In another related aspect, the invention provides an antibody that binds immunologically to an EPS8L2 protein for detecting endometrial cancer. In a related aspect the invention provides an EPS8L2 polypeptide for generating an antibody. In yet another related aspect, the invention provides an EPS8L2 polypeptide for generating an immune response against the marker.

[0264] In one embodiment, the invention provides a FASTKD1 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a FASTKD1 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a FASTKD1 nucleic acid for detecting endometrial cancer.

[0265] In another related aspect, the invention provides an antibody that binds immunologically to a FASTKD1 protein for detecting endometrial cancer. In a related aspect the invention provides a FASTKD1 polypeptide for generating an antibody. In yet another related aspect, the invention provides a FASTKD1 polypeptide for generating an immune response against the marker.

[0266] In one embodiment, the invention provides a GMIP nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a GMIP nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a GMIP nucleic acid for detecting endometrial cancer.

[0267] In another related aspect, the invention provides an antibody that binds immunologically to a GMIP protein for detecting endometrial cancer. In a related aspect the invention provides a GMIP polypeptide for generating an antibody. In yet another related aspect, the invention provides a GMIP polypeptide for generating an immune response against the marker.

[0268] In one embodiment, the invention provides an IKBKE nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying an IKBKE nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to an IKBKE nucleic acid for detecting endometrial cancer.

[0269] In another related aspect, the invention provides an antibody that binds immunologically to an IKBKE protein for detecting endometrial cancer. In a related aspect the invention provides an IKBKE polypeptide for generating an antibody. In yet another related aspect, the invention provides an IKBKE polypeptide for generating an immune response against the marker.

[0270] In one embodiment, the invention provides a P2RX4 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a P2RX4 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a P2RX4 nucleic acid for detecting endometrial cancer.

[0271] In another related aspect, the invention provides an antibody that binds immunologically to a P2RX4 protein for detecting endometrial cancer. In a related aspect the invention provides a P2RX4 polypeptide for generating an antibody. In yet another related aspect, the invention provides a P2RX4 polypeptide for generating an immune response against the marker.

[0272] In one embodiment, the invention provides a P4HB nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a P4HB nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a P4HB nucleic acid for detecting endometrial cancer.

[0273] In another related aspect, the invention provides an antibody that binds immunologically to a P4HB protein for detecting endometrial cancer. In a related aspect the invention provides a P4HB polypeptide for generating an antibody. In yet another related aspect, the invention provides a P4HB polypeptide for generating an immune response against the marker.

[0274] In one embodiment, the invention provides a PHKG2 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a PHKG2 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a PHKG2 nucleic acid for detecting endometrial cancer.

[0275] In another related aspect, the invention provides an antibody that binds immunologically to a PHKG2 protein for detecting endometrial cancer. In a related aspect the invention provides a PHKG2 polypeptide for generating an antibody. In yet another related aspect, the invention provides a PHKG2 polypeptide for generating an immune response against the marker.

[0276] In one embodiment, the invention provides a PPFIBP2 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a PPFIBP2 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a PPFIBP2 nucleic acid for detecting endometrial cancer.

[0277] In another related aspect, the invention provides an antibody that binds immunologically to a PPFIBP2 protein for detecting endometrial cancer. In a related aspect the invention provides a PPFIBP2 polypeptide for generating an antibody. In yet another related aspect, the invention provides a PPFIBP2 polypeptide for generating an immune response against the marker.

[0278] In one embodiment, the invention provides a PPP1R16A nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a PPP1R16A nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a PPP1R16A nucleic acid for detecting endometrial cancer.

[0279] In another related aspect, the invention provides an antibody that binds immunologically to a PPP1R16A protein for detecting endometrial cancer. In a related aspect the invention provides a PPP1R16A polypeptide for generating an antibody. In yet another related aspect, the invention provides a PPP1R16A polypeptide for generating an immune response against the marker.

[0280] In one embodiment, the invention provides a RASSF7 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a RASSF7 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a RASSF7 nucleic acid for detecting endometrial cancer.

[0281] In another related aspect, the invention provides an antibody that binds immunologically to a RASSF7 protein for detecting endometrial cancer. In a related aspect the invention provides a RASSF7 polypeptide for generating an antibody. In yet another related aspect, the invention provides a RASSF7 polypeptide for generating an immune response against the marker.

[0282] In one embodiment, the invention provides a RNF183 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a RNF183 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a RNF183 nucleic acid for detecting endometrial cancer.

[0283] In another related aspect, the invention provides an antibody that binds immunologically to a RNF183 protein for detecting endometrial cancer. In a related aspect the invention provides a RNF183 polypeptide for generating an antibody. In yet another related aspect, the invention provides a RNF183 polypeptide for generating an immune response against the marker.

[0284] In one embodiment, the invention provides a SIRT6 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a SIRT6 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a SIRT6 nucleic acid for detecting endometrial cancer.

[0285] In another related aspect, the invention provides an antibody that binds immunologically to a SIRT6 protein for detecting endometrial cancer. In a related aspect the invention provides a SIRT6 polypeptide for generating an antibody. In yet another related aspect, the invention provides a SIRT6 polypeptide for generating an immune response against the marker.

[0286] In one embodiment, the invention provides a TJP3 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a TJP3 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a TJP3 nucleic acid for detecting endometrial cancer.

[0287] In another related aspect, the invention provides an antibody that binds immunologically to a TJP3 protein for detecting endometrial cancer. In a related aspect the invention provides a TJP3 polypeptide for generating an antibody. In yet another related aspect, the invention provides a TJP3 polypeptide for generating an immune response against the marker.

[0288] In one embodiment, the invention provides an EFEMP2 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying an EFEMP2 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to an EFEMP2 nucleic acid for detecting endometrial cancer.

[0289] In another related aspect, the invention provides an antibody that binds immunologically to an EFEMP2 protein for detecting endometrial cancer. In a related aspect the invention provides an EFEMP2 polypeptide for generating an antibody. In yet another related aspect, the invention provides an EFEMP2 polypeptide for generating an immune response against the marker.

[0290] In one embodiment, the invention provides a SOCS2 nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a SOCS2 nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a SOCS2 nucleic acid for detecting endometrial cancer.

[0291] In another related aspect, the invention provides an antibody that binds immunologically to a SOCS2 protein for detecting endometrial cancer. In a related aspect the invention provides a SOCS2 polypeptide for generating an antibody. In yet another related aspect, the invention provides a SOCS2 polypeptide for generating an immune response against the marker.

[0292] In one embodiment, the invention provides a DCN nucleic acid for detecting endometrial cancer. In a related aspect, the invention provides primers for amplifying a DCN nucleic acid for detecting endometrial cancer. In another related aspect the invention provides a probe that can hybridize to a DCN nucleic acid for detecting endometrial cancer.

[0293] In another related aspect, the invention provides an antibody that binds immunologically to a DCN protein for detecting endometrial cancer. In a related aspect the invention provides a DCN polypeptide for generating an antibody. In yet another related aspect, the invention provides a DCN polypeptide for generating an immune response against the marker.

[0294] Kits

[0295] The invention also provides kits for detecting one or more of the biomarkers of Table 1. In one embodiment, the kit is useful for detecting and/or diagnosing a gynecological cancer. In another embodiment, the kit is useful for detecting and/or diagnosing endometrial cancer. In one aspect, the kit contains reagents for detecting CGN. In one aspect, the kit contains means for detecting CGN. In one aspect, the kit contains reagents for detecting AP1M2. In one aspect, the kit contains means for detecting AP1M2. In one aspect, the kit contains reagents for detecting EPS8L2. In one aspect, the kit contains means for detecting EPS8L2. In one aspect, the kit contains reagents for detecting IKBKE. In one aspect, the kit contains means for detecting IKBKE. In one aspect, the kit contains reagents for detecting PPP1R16A. In one aspect, the kit contains means for detecting PPP1R16A. In one aspect, the kit contains reagents for detecting RASSF7. In one aspect, the kit contains means for detecting RASSF7. In one aspect, the kit contains reagents for detecting TJP3. In one aspect, the kit contains means for detecting TJP3. In one aspect, the kit contains reagents for detecting P2RX4. In one aspect, the kit contains means for detecting P2RX4. In one aspect, the kit contains reagents for detecting RNF183. In one aspect, the kit contains means for detecting RNF183. In one aspect, the kit contains reagents for detecting GMIP. In one aspect, the kit contains means for detecting GMIP. In one aspect, the kit contains reagents for detecting PHKG2. In one aspect, the kit contains means for detecting PHKG2. In one aspect, the kit contains reagents for detecting P4HB. In one aspect, the kit contains means for detecting P4HB. In one aspect, the kit contains reagents for detecting PPFIBP2. In one aspect, the kit contains means for detecting PPFIBP2. In one aspect, the kit contains reagents for detecting FASTKD1. In one aspect, the kit contains means for detecting FASTKD1. In one aspect, the kit contains reagents for detecting DDR1. In one aspect, the kit contains means for detecting DDR1. In one aspect, the kit contains reagents for detecting SIRT6. In one aspect, the kit contains means for detecting SIRT6. In one aspect, the kit contains reagents for detecting ACAA1. In one aspect, the kit contains means for detecting ACAA1. In one aspect, the kit contains reagents for detecting DCN. In one aspect, the kit contains means for detecting DCN. In one aspect, the kit contains reagents for detecting SOCS2. In one aspect, the kit contains means for detecting SOCS2. In one aspect, the kit contains reagents for detecting EFEMP2. In one aspect, the kit contains means for detecting EFEMP2.

[0296] In one aspect, the kit contains reagents for detecting from 2 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 2 to 20 of the biomarkers of Table 1. In one aspect, the kit contains reagents for detecting from 3 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 3 to 20 of the biomarkers of Table 1. In one aspect, the kit contains reagents for detecting from 4 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 4 to 20 of the biomarkers of Table 1. In one aspect, the kit contains reagents for detecting from 5 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 5 to 20 of the biomarkers of Table 1. In one aspect, the kit contains reagents for detecting from 6 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 6 to 20 of the biomarkers of Table 1. In one aspect, the kit contains reagents for detecting from 7 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 7 to 20 of the biomarkers of Table 1. In one aspect, the kit contains reagents for detecting from 8 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 8 to 20 of the biomarkers of Table 1. In one aspect, the kit contains reagents for detecting from 9 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 9 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 10 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 10 to 20 of the biomarkers of Table 1. In one aspect, the kit contains means for detecting from 15 to 20 of the biomarkers of Table 1. In one aspect, the kit comprises reagents for the RT-PCR evaluation of from 1 to 20 of the biomarkers of Table 1. In one aspect, the kit comprises means for the RT-PCR evaluation of from 1 to 20 of the biomarkers of Table 1. In one aspect, the kit comprises reagents for microarray evaluation of from 1 to 20 of the biomarkers of Table 1. In one aspect, the kit comprises means for microarray evaluation of from 1 to 20 of the biomarkers of Table 1. In one aspect, the kit comprises reagents for antibody-based evaluation of from 1 to 20 of the biomarkers of Table 1. In one aspect, the kit comprises means for antibody-based evaluation of from 1 to 20 of the biomarkers of Table 1. In one aspect, the kit has reagents for detecting different biomarkers in addition to one or more of those listed in Table 1. In one aspect, the kit has means for detecting different biomarkers in addition to the 1 to 20 of those listed in Table 1. In one aspect, the kit has reagents for multiplex PCR of from 2 to 20 markers of Table 1. In one aspect, the kit has means for multiplex PCR of from 2 to 20 markers of Table 1.

[0297] In some aspects, the kit has a device for obtaining a sample for analysis. In one aspect the device is a pipelle. In another aspect, the device is as described in U.S. Pat. No. 7,207,951, Issued Apr. 24, 2007, which is incorporated by herein reference in its entirety. In another aspect, the device is curettage. In another aspect, the device is a brush. One example of a brush device is the tao brush

[0298] In some aspects, the kit has an agent to stabilizing the samples obtained from the patient. For example, in a specific aspect, the agent is a buffer for stabilizing the sample obtained from the patient comprises an RNA preserving solution. In another aspect, the agent is useful for stabilizing blood or serum samples.

[0299] Diagnostic Antibodies to the Biomarkers of Table 1

[0300] Diagnostic antibodies to one or more of the biomarkers of Table 1 (also referred to as a target protein) for diagnostic uses can be obtained in any number of ways. Furthermore, antibodies to some of the biomarkers of Table 1 are commercially available or described in the literature. These known antibodies can be used in the methods of the invention and/or as the basis of engineering new antibodies. Phage display techniques can be used to generate antibodies to one or more of the biomarkers of Table 1. Standard hybridoma technologies can be used to generate antibodies to one or more of the biomarkers of Table 1. Antibodies to some of the biomarkers of Table 1 are known in the art see the examples. In some aspects, the antibody to one or more of the biomarkers of Table 1 is derived from an animal source (e.g., mouse, rat, or rabbit).

[0301] Polyclonal Antibodies

[0302] The target protein antibodies may comprise polyclonal antibodies. Methods of preparing polyclonal antibodies are known to the skilled artisan. Polyclonal antibodies can be raised in a mammal, for example, by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and/or adjuvant t will be injected in the mammal by multiple subcutaneous or intraperitoneal injections. The immunizing agent may include the target protein polypeptide (or fragment thereof) or a fusion protein thereof. It may be useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Examples of adjuvants which may be employed include Freund's complete adjuvant and M PL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate). The immunization protocol may be selected by one skilled in the art without undue experimentation.

[0303] Monoclonal Antibodies

[0304] The target protein antibodies may, alternatively, be monoclonal antibodies. Monoclonal antibodies may be prepared using hybridoma methods, such as those described by Kohler and Milstein (1975) Nature 256:495. In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes may be immunized in vitro.

[0305] The immunizing agent will typically include the target protein polypeptide (or fragment thereof) or a fusion protein thereof. Generally, either peripheral blood lymphocytes ("PBLs") are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103). Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells.

[0306] Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, Calif. and the American Type Culture Collection, Manassas, Va. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor (1984) J. Immunol. 133:3001; Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).

[0307] The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against target protein. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard (1980) Anal. Biochem. 107:220.

[0308] After the desired hybridoma cells are identified, the clones may be subcloned by limiting dilution procedures and grown by standard methods [Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103]. Suitable culture media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells may be grown in vivo as ascites in a mammal.

[0309] The monoclonal antibodies secreted by the subclones may be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.

[0310] The monoclonal antibodies may also be made by recombinant DNA methods, such as those described in U.S. Pat. No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a preferred source of such DNA. Once isolated, the DNA may be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also may be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences [U.S. Pat. No. 4,816,567; Morrison et al., supra] or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody.

[0311] The antibodies may be monovalent antibodies. Methods for preparing monovalent antibodies are well known in the art. For example, one method involves recombinant expression of immunoglobulin light chain and modified heavy chain. The heavy chain is truncated generally at any point in the Fc region so as to prevent heavy chain crosslinking. Alternatively, the relevant cysteine residues are substituted with another amino acid residue or are deleted so as to prevent crosslinking.

[0312] In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce fragments thereof, particularly, Fab fragments, can be accomplished using routine techniques known in the art.

[0313] Phage Display

[0314] Antibodies to the biomarkers of the invention can also be made by using combinatorial libraries to screen for synthetic antibody clones with the desired activity or activities. In principle, synthetic antibody clones are selected by screening phage libraries containing phage that display various fragments of antibody variable region (Fv) fused to phage coat protein. Such phage libraries are panned by affinity chromatography against the desired antigen. Clones expressing Fv fragments capable of binding to the desired antigen are adsorbed to the antigen and thus separated from the non-binding clones in the library. The binding clones are then eluted from the antigen, and can be further enriched by additional cycles of antigen adsorption/elution. Antibodies to the biomarkers of the invention can be obtained by designing a suitable antigen screening procedure to select for the phage clone of interest followed by construction of a full length antibody clone using the Fv sequences from the phage clone of interest and suitable constant region (Fc) sequences described in Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, NIH Publication 91-3242, Bethesda Md. (1991), vols. 1-3.

[0315] Antibody Conjugates

[0316] The antibodies (and fragments thereof) of the invention can be conjugated to molecules for diagnostic purposes. For example, an antibody to a biomarker of Table 1 can be conjugated to a detectable label (e.g., for imaging purposes) for diagnosing or detecting endometrial cancer. Suitable detectable markers include, but are not limited to, a radioisotope, a nanoparticle, a fluorescent compound, a bioluminescent compound, chemiluminescent compound, a metal chelator or an enzyme. Techniques for conjugating diagnostic agents to antibodies are well known (Holmes et al. (2001) Curr Protoc Cytom. May; Chapter 4:Unit 4.2; Kumar et al (2008) ACS Nano. March; 2(3):449-56; Rosenthal et al. (2006) Laryngoscope September; 116(9):1636-41). Additionally kits for conjugating agents to diagnostic antibodies are commercially available.

[0317] Data and Information

[0318] In one aspect of the invention, the present invention relates to methods for comparing and compiling data wherein the data is stored in electronic or paper format. Electronic format can be selected from the group consisting of electronic mail, disk, compact disk (CD), digital versatile disk (DVD), memory card, memory chip, ROM or RAM, magnetic optical disk, tape, video, video clip, microfilm, internet, shared network, shared server and the like; wherein data is displayed, transmitted or analyzed via electronic transmission, video display, telecommunication, or by using any of the above stored formats; wherein data is compared and compiled at the site of sampling specimens or at a location where the data is transported following a process as described above. The data of this embodiment is information regarding the results of the analysis of the biomarkers of Table 1.

[0319] The biomarkers, reagents, targets, assays, tests, inquiries and methodologies described herein can be employed in a variety of contexts, including diagnostic discovery, diagnostic development, safety and efficacy monitoring, comparative studies, marketing and the like. The information provided by the invention can be communicated to regulators, physicians and other healthcare providers, manufacturers, owners, investors, patients, and/or the general public. This information and the like can be used in exploratory research, pre-clinical and clinical settings, labeling, production, advertising, and sales, for example.

DEFINITIONS

[0320] As used herein an "ACAA1 biomarker" refers to an "ACAA1 nucleic acid" or an "ACAA1 protein" that can be specifically detected. An ACAA1 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human ACAA1 gene or a fragment thereof. For example, an ACAA1 nucleic acid can be a cDNA, or fragment thereof, corresponding to an ACAA1 mRNA molecule. An ACAA1 protein refers to a protein (or fragment thereof) encoded or expressed by the ACAA1 gene. Examples of ACAA1 biomarkers are given in the examples as well as some reagents useful for detecting ACAA1 biomarkers, nucleic acids, and proteins.

[0321] As used herein an "AP1M2 biomarker" refers to an "AP1M2 nucleic acid" or an "AP1M2 protein" that can be specifically detected. An AP1M2 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human AP1M2 gene or a fragment thereof. For example, an AP1M2 nucleic acid can be a cDNA, or fragment thereof, corresponding to an AP1M2 mRNA molecule. An AP1M2 protein refers to a protein (or fragment thereof) encoded or expressed by the AP1M2 gene. Examples of AP1M2 biomarkers are given in the examples as well as some reagents useful for detecting AP1M2 biomarkers, nucleic acids, and proteins.

[0322] As used herein a "CGN biomarker" refers to a "CGN nucleic acid" or a "CGN protein" that can be specifically detected. A CGN nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human CGN gene or a fragment thereof. For example, a CGN nucleic acid can be a cDNA, or fragment thereof, corresponding to a CGN mRNA molecule. A CGN protein refers to a protein (or fragment thereof) encoded or expressed by the CGN gene. Examples of CGN biomarkers are given in the examples as well as some reagents useful for detecting CGN biomarkers, nucleic acids, and proteins.

[0323] As used herein a "DDR1 biomarker" refers to a "DDR1 nucleic acid" or a "DDR1 protein" that can be specifically detected. A DDR1 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human DDR1 gene or a fragment thereof. For example, a DDR1 nucleic acid can be a cDNA, or fragment thereof, corresponding to a DDR1 mRNA molecule. A DDR1 protein refers to a protein (or fragment thereof) encoded or expressed by the DDR1 gene. Examples of DDR1 biomarkers are given in the examples as well as some reagents useful for detecting DDR1 biomarkers, nucleic acids, and proteins.

[0324] As used herein an "EPS8L2 biomarker" refers to an "EPS8L2 nucleic acid" or an "EPS8L2 protein" that can be specifically detected. An EPS8L2 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human EPS8L2 gene or a fragment thereof. For example, an EPS8L2 nucleic acid can be a cDNA, or fragment thereof, corresponding to an EPS8L2 mRNA molecule. An EPS8L2 protein refers to a protein (or fragment thereof) encoded or expressed by the EPS8L2 gene. Examples of EPS8L2 biomarkers are given in the examples as well as some reagents useful for detecting EPS8L2 biomarkers, nucleic acids, and proteins.

[0325] As used herein a "FASTKD1 biomarker" refers to a "FASTKD1 nucleic acid" or an "FASTKD1 protein" that can be specifically detected. A FASTKD1 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human FASTKD1 gene or a fragment thereof. For example, a FASTKD1 nucleic acid can be a cDNA, or fragment thereof, corresponding to an FASTKD1 mRNA molecule. A FASTKD1 protein refers to a protein (or fragment thereof) encoded or expressed by the FASTKD1 gene. Examples of FASTKD1 biomarkers are given in the examples as well as some reagents useful for detecting FASTKD1 biomarkers, nucleic acids, and proteins.

[0326] As used herein a "GMIP biomarker" refers to an "GMIP nucleic acid" or an "GMIP protein" that can be specifically detected. An GMIP nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human GMIP gene or a fragment thereof. For example, a GMIP nucleic acid can be a cDNA, or fragment thereof, corresponding to a GMIP mRNA molecule. A GMIP protein refers to a protein (or fragment thereof) encoded or expressed by the GMIP gene. Examples of GMIP biomarkers are given in the examples as well as some reagents useful for detecting GMIP biomarkers, nucleic acids, and proteins.

[0327] As used herein an "IKBKE biomarker" refers to an "IKBKE nucleic acid" or an "IKBKE protein" that can be specifically detected. An IKBKE nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human IKBKE gene or a fragment thereof. For example, an IKBKE nucleic acid can be a cDNA, or fragment thereof, corresponding to an IKBKE mRNA molecule. An IKBKE protein refers to a protein (or fragment thereof) encoded or expressed by the IKBKE gene. Examples of IKBKE biomarkers are given in the examples as well as some reagents useful for detecting IKBKE biomarkers, nucleic acids, and proteins.

[0328] As used herein a "P2RX4 biomarker" refers to a "P2RX4 nucleic acid" or an "P2RX4 protein" that can be specifically detected. A P2RX4 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human P2RX4 gene or a fragment thereof. For example, a P2RX4 nucleic acid can be a cDNA, or fragment thereof, corresponding to a P2RX4 mRNA molecule. A P2RX4 protein refers to a protein (or fragment thereof) encoded or expressed by the P2RX4 gene. Examples of P2RX4 biomarkers are given in the examples as well as some reagents useful for detecting P2RX4 biomarkers, nucleic acids, and proteins.

[0329] As used herein a "P4HB biomarker" refers to a "P4HB nucleic acid" or a "P4HB protein" that can be specifically detected. A P4HB nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human P4HB gene or a fragment thereof. For example, a P4HB nucleic acid can be a cDNA, or fragment thereof, corresponding to a P4HB mRNA molecule. A P4HB protein refers to a protein (or fragment thereof) encoded or expressed by the P4HB gene. Examples of P4HB biomarkers are given in the examples as well as some reagents useful for detecting P4HB biomarkers, nucleic acids, and proteins.

[0330] As used herein a "PHKG2 biomarker" refers to a "PHKG2 nucleic acid" or an "PHKG2 protein" that can be specifically detected. A PHKG2 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human AP1M2 gene or a fragment thereof. For example, a PHKG2 nucleic acid can be a cDNA, or fragment thereof, corresponding to a PHKG2 mRNA molecule. A PHKG2 protein refers to a protein (or fragment thereof) encoded or expressed by the PHKG2 gene. Examples of PHKG2 biomarkers are given in the examples as well as some reagents useful for detecting PHKG2 biomarkers, nucleic acids, and proteins.

[0331] As used herein a "PPFIBP2 biomarker" refers to a "PPFIBP2 biomarker nucleic acid" or a "PPFIBP2 biomarker protein" that can be specifically detected. A PPFIBP2 biomarker nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human PPFIBP2 biomarker gene or a fragment thereof. For example, a PPFIBP2 biomarker nucleic acid can be a cDNA, or fragment thereof, corresponding to an PPFIBP2 biomarker mRNA molecule. A PPFIBP2 biomarker protein refers to a protein (or fragment thereof) encoded or expressed by the PPFIBP2 biomarker gene. Examples of PPFIBP2 biomarker biomarkers are given in the examples as well as some reagents useful for detecting PPFIBP2 biomarker biomarkers, nucleic acids, and proteins.

[0332] As used herein a "PPP1R16A biomarker" refers to a "PPP1R16A nucleic acid" or a "PPP1R16A protein" that can be specifically detected. A PPP1R16A nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human PPP1R16A gene or a fragment thereof. For example, a PPP1R16A nucleic acid can be a cDNA, or fragment thereof, corresponding to a PPP1R16A mRNA molecule. A PPP1R16A protein refers to a protein (or fragment thereof) encoded or expressed by the PPP1R16A gene. Examples of PPP1R16A biomarkers are given in the examples as well as some reagents useful for detecting PPP1R16A biomarkers, nucleic acids, and proteins.

[0333] As used herein a "TJP3 biomarker" refers to a "TJP3 nucleic acid" or a "TJP3 protein" that can be specifically detected. A TJP3 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human TJP3 gene or a fragment thereof. For example, a TJP3 nucleic acid can be a cDNA, or fragment thereof, corresponding to a TJP3 mRNA molecule. A TJP3 protein refers to a protein (or fragment thereof) encoded or expressed by the TJP3 gene. Examples of TJP3 biomarkers are given in the examples as well as some reagents useful for detecting TJP3 biomarkers, nucleic acids, and proteins.

[0334] As used herein an "RASSF7 biomarker" refers to an "RASSF7 nucleic acid" or an "RASSF7 protein" that can be specifically detected. An RASSF7 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human RASSF7 gene or a fragment thereof. For example, an RASSF7 nucleic acid can be a cDNA, or fragment thereof, corresponding to an RASSF7 mRNA molecule. An RASSF7 protein refers to a protein (or fragment thereof) encoded or expressed by the RASSF7 gene. Examples of RASSF7 biomarkers are given in the examples as well as some reagents useful for detecting RASSF7 biomarkers, nucleic acids, and proteins.

[0335] As used herein a "RNF183 biomarker" refers to a "RNF183 nucleic acid" or a "RNF183 protein" that can be specifically detected. A RNF183 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human RNF183 gene or a fragment thereof. For example, a RNF183 nucleic acid can be a cDNA, or fragment thereof, corresponding to a RNF183 mRNA molecule. A RNF183 protein refers to a protein (or fragment thereof) encoded or expressed by the RNF183 gene. Examples of RNF183 biomarkers are given in the examples as well as some reagents useful for detecting RNF183 biomarkers, nucleic acids, and proteins.

[0336] As used herein a "SIRT6 biomarker" refers to a "SIRT6 nucleic acid" or a "SIRT6 protein" that can be specifically detected. A SIRT6 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human SIRT6 gene or a fragment thereof. For example, a SIRT6 nucleic acid can be a cDNA, or fragment thereof, corresponding to a SIRT6 mRNA molecule. A SIRT6 protein refers to a protein (or fragment thereof) encoded or expressed by the SIRT6 gene. Examples of SIRT6 biomarkers are given in the examples as well as some reagents useful for detecting SIRT6 biomarkers, nucleic acids, and proteins.

[0337] As used herein a "DCN biomarker" refers to a "DCN nucleic acid" or a "DCN protein" that can be specifically detected. A DCN nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human DCN gene or a fragment thereof. For example, a DCN nucleic acid can be a cDNA, or fragment thereof, corresponding to a DCN mRNA molecule. A DCN protein refers to a protein (or fragment thereof) encoded or expressed by the DCN gene. Examples of LSR biomarkers are given in the examples as well as some reagents useful for detecting DCN biomarkers, nucleic acids, and proteins.

[0338] As used herein a "SOCS2 biomarker" refers to a "SOCS2 nucleic acid" or a "SOCS2 protein" that can be specifically detected. A SOCS2 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human SOCS2 gene or a fragment thereof. For example, a SOCS2 nucleic acid can be a cDNA, or fragment thereof, corresponding to a SOCS2 mRNA molecule. A SOCS2 protein refers to a protein (or fragment thereof) encoded or expressed by the SOCS2 gene. Examples of SOCS2 biomarkers are given in the examples as well as some reagents useful for detecting SOCS2 biomarkers, nucleic acids, and proteins.

[0339] As used herein an "EFEMP2 biomarker" refers to an "EFEMP2 nucleic acid" or an "EFEMP2 protein" that can be specifically detected. An EFEMP2 nucleic acid can be a RNA molecule, DNA molecule, or other nucleic acid that corresponds to the human EFEMP2 gene or a fragment thereof. For example, an EFEMP2 nucleic acid can be a cDNA, or fragment thereof, corresponding to an EFEMP2 mRNA molecule. An EFEMP2 protein refers to a protein (or fragment thereof) encoded or expressed by the EFEMP2 gene. Examples of EFEMP2 biomarkers are given in the examples as well as some reagents useful for detecting EFEMP2 biomarkers, nucleic acids, and proteins.

[0340] As used herein, the term "sensitivity" refers to the proportion of reference test positive (diseased) subjects who test positive with the screening test.

[0341] As used herein, the term "specificity" refers to the proportion of reference test negative (healthy) subjects who test negative with the screening test.

[0342] As used herein, the term "secretory phase" refers to a phase of the menstrual cycle that is distinguishable from the other phases of the menstrual cycle using standard procedures in the art, e.g., pathological examination of tissue obtained from endometrium or uterus. Secretory phase is associated with bleeding (menstruation).

[0343] As used herein, the term "ROC" or "receiver operator characteristic" refers to a graphical plot of sensitivity vs. (1-specificity) or in other words a plot of true positive rate versus fraction of false positives. The area under the ROC, or AUROC, curve can range from 0 to 1. An area under the ROC curve of 1 is a perfect test or separation of groups while an area under the ROC of 0.5 indicates that the classifier is essentially unable to separate the groups and is therefore not useful.

[0344] A "cancer" in an animal refers to the presence of cells possessing characteristics typical of cancer-causing cells, for example, uncontrolled proliferation, loss of specialized functions, immortality, significant metastatic potential, significant increase in anti-apoptotic activity, rapid growth and proliferation rate, and certain characteristic morphology and cellular markers.

[0345] The phrase "detecting a cancer" or "diagnosing a cancer" refers to determining the presence or absence of cancer or a precancerous condition in an animal. "Detecting a cancer" also can refer to obtaining evidence regarding the likelihood of the presence of precancerous or cancerous cells in the animal or assessing the predisposition of a patient to the development of a cancer. Detecting a cancer can be accomplished using the methods of this invention alone, in combination with other methods, or in light of other information regarding the state of health of the animal.

[0346] A "tumor," as used herein, refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all precancerous and cancerous cells and tissues.

[0347] The term "precancerous" refers to cells or tissues having characteristics relating to changes that may lead to malignancy or cancer.

[0348] In general, a "gene" is a region on the genome that is capable of being transcribed to an RNA that either has a regulatory function, a catalytic function, and/or encodes a protein. An eukaryotic gene typically has introns and exons, which may organize to produce different RNA splice variants that encode alternative versions of a mature protein. The skilled artisan will appreciate that the present invention encompasses all encoding transcripts that may be found, including splice variants, allelic variants and transcripts that occur because of alternative promoter sites or alternative poly-adenylation sites of the biomarkers as listed in Table 1. A "full-length" gene or RNA therefore encompasses any naturally occurring splice variants, allelic variants, other alternative transcripts, splice variants generated by recombinant technologies which bear the same function as the naturally occurring variants, and the resulting RNA molecules. A "fragment" of a gene, including an oncogene, can be any portion from the gene, which may or may not represent a functional domain, for example, a catalytic domain, a DNA binding domain, etc. A fragment may preferably include nucleotide sequences that encode for at least 25 contiguous amino acids, and preferably at least about 30, 40, 50, 60, 65, 70, 75 or more contiguous amino acids or any integer thereabout or therebetween. In some aspects of the invention, the skilled artisan recognizes that the term gene is used interchangeably with the term "locus", which refers more generically to a region of genomic DNA regardless if it codes for RNA, protein, or a regulatory element.

[0349] A "differentially expressed gene transcript", as used herein, refers to a gene, transcript that is found at a different level in different cell or tissue types of an organism having a tumor or cancer, compared to the level or state of the gene transcript found in the cells of the same tissue in a healthy organism, or in the cells of the same tissue in the same organism. Multiple copies of gene transcripts may be found in an organism having the tumor or cancer, while fewer copies of the same gene transcript are found in a healthy organism or healthy cells of the same tissue in the same organism, or vice-versa for underexpressed genes. In general, differentially expressed transcripts are those which when measured in an affected sample or sample from an affected patient have a detectably different level of expression as compared to a control value which is representative of a non-affected sample or sample from a non-affected patient. Examples of differential expression include a change of 10% or more, 20% or more 30% or more, 40% or more, or 50% or more in affected as compared to non-affected.

[0350] As used herein the term "polypeptide" means a sequence of amino acids joined together by peptide bonds. The amino acid sequence of the polypeptide can determined by the sequence of the DNA bases which encode the amino acids of the polypeptide chain. The polypeptides described herein include, but are not limited to, complete proteins, fragments of complete proteins, epitopes of proteins etc. As used herein the term polypeptide, peptide, and protein refer to molecule having two or more amino acid residues (natural or unnatural) joined together by one or more peptide bonds.

[0351] A "differentially expressed gene," can be a target, fingerprint, or pathway gene. For example, a "fingerprint gene", as used herein, refers to a differentially expressed gene whose expression pattern can be used as a prognostic or diagnostic marker for the evaluation of tumors and cancers, or which can be used to identify compounds useful for the treatment of tumors and cancers, for example, endometrial cancer. Fingerprint genes can be one or more genes (or corresponding biomarkers e.g., protein) corresponding to the biomarkers of Table 1.

[0352] A "fingerprint pattern", as used herein, refers to a pattern generated when the expression pattern of a series (which can range from two up to all the fingerprint genes that exist for a given state) of fingerprint genes is determined. A fingerprint pattern also may be referred to as n "profile". A fingerprint pattern or expression profile having from 1 to 20 of the biomarkers of Table 1 can be used in the same diagnostic, prognostic, and methods of the invention.

[0353] "Pathway genes", as used herein, are genes that encode proteins or polypeptides that interact with other gene products involved in tumors and cancers. Pathway genes also can exhibit target gene and/or fingerprint gene characteristics.

[0354] A "detectable" RNA expression level, as used herein, means a level that is detectable by standard techniques currently known in the art or those that become standard at some future time, and include for example, differential display, RT (reverse transcriptase)-coupled polymerase chain reaction (PCR), Northern Blot, and/or RNase protection analyses.

[0355] The nucleic acid molecules of the invention, for example, those corresponding to one or more biomarkers of Table 1, and its subsequences/alternative transcripts, can be inserted into a vector, as described below, which will facilitate expression of the insert. The nucleic acid molecules and the polypeptides they encode can be used directly as diagnostic agents, or can be used (directly in the case of the polypeptide or indirectly in the case of a nucleic acid molecule) to generate antibodies that, in turn, are clinically useful as a diagnostic agent. Accordingly, vectors containing the nucleic acids of the invention, cells transfected with these vectors, the polypeptides expressed, and antibodies generated against either the entire polypeptide or an antigenic fragment thereof, are among the aspects of the invention.

[0356] An "isolated DNA molecule" is a fragment of DNA that has been separated from the chromosomal or genomic DNA of an organism. Isolation also is defined to connote a degree of separation from original source or surroundings.

[0357] "Complementary DNA" (cDNA), often referred to as "copy DNA", is a single-stranded DNA molecule that is formed from an mRNA template by the enzyme reverse transcriptase. Those skilled in the art also use the term "cDNA" to refer to a double-stranded DNA molecule that comprises such a single-stranded DNA molecule and its complement DNA strand.

[0358] The term "expression" refers to the biosynthesis of a gene product.

[0359] A "cloning vector" is a nucleic acid molecule, for example, a plasmid, cosmid or bacteriophage that has the capability of replicating autonomously in a host cell. Cloning vectors typically contain (i) one or a small number of restriction endonuclease recognition sites at which foreign DNA sequences can be inserted in a determinable fashion without loss of an essential biological function of the vector, and (ii) a marker gene that is suitable for use in the identification and selection of cells transformed or transfected with the cloning vector. Marker genes include, but are not limited to, genes that provide tetracycline resistance or ampicillin resistance.

[0360] An "expression vector" is a nucleic acid construct, generated recombinantly or synthetically, bearing a series of specified nucleic acid elements that enable transcription of a particular gene in a host cell. Typically, gene expression is placed under the control of certain regulatory elements, including constitutive or inducible promoters, tissue-preferred regulatory elements, and enhancers.

[0361] A "recombinant host" may be any prokaryotic or eukaryotic cell that contains either a cloning vector or expression vector. This term also includes those prokaryotic or eukaryotic cells that have been genetically engineered to contain the cloned gene(s) in the chromosome or genome of the host cell.

[0362] The term "operably linked" is used to describe the connection between regulatory elements and a gene or its coding region. That is, gene expression is typically placed under the control of certain regulatory elements, including constitutive or inducible promoters, tissue-specific regulatory elements, and enhancers. Such a gene or coding region is said to be "operably linked to" or "operatively linked to" or "operably associated with" the regulatory elements, meaning that the gene or coding region is controlled or influenced by the regulatory element.

[0363] "Sequence homology" is used to describe the sequence relationships between two or more nucleic acids, polynucleotides, proteins, or polypeptides, and is understood in the context of and in conjunction with the terms including: (a) reference sequence, (b) comparison window, (c) sequence identity, (d) percentage of sequence identity, and (e) substantial identity or "homologous."

[0364] A "reference sequence" is a defined sequence used as a basis for sequence comparison. A reference sequence may be a subset of or the entirety of a specified sequence; for example, a segment of a full-length cDNA or gene sequence, or the complete cDNA or gene sequence. For polypeptides, the length of the reference polypeptide sequence can be chosen from at least about 16 amino acids, at least about 20 amino acids, at least about 25 amino acids, and about 35 amino acids, about 50 amino acids, or about 100 amino acids. For nucleic acids, the length of the reference nucleic acid sequence can be chosen from at least about 50 nucleotides, at least about 60 nucleotides, at least about 75 nucleotides, and about 100 nucleotides or about 300 nucleotides or any integer thereabout or there between.

[0365] A "comparison window" includes reference to a contiguous and specified segment of a polynucleotide sequence, wherein the polynucleotide sequence may be compared to a reference sequence and wherein the portion of the polynucleotide sequence in the comparison window may comprise additions, substitutions, or deletions (i.e., gaps) compared to the reference sequence (which does not comprise additions, substitutions, or deletions) for optimal alignment of the two sequences. Generally, the comparison window is at least 20 contiguous nucleotides in length, and optionally can be 30, 40, 50, 100, or longer. Those of skill in the art understand that to avoid a misleadingly high similarity to a reference sequence due to inclusion of gaps in the polynucleotide sequence a gap penalty is typically introduced and is subtracted from the number of matches.

[0366] Methods of alignment of sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison may be conducted by the local homology algorithm of Smith and Waterman (1981) Adv. Appl. Math., 2: 482; by the homology alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol., 48: 443; by the search for similarity method of Pearson and Lipman (1988) Proc. Natl. Acad. Sci. USA, 8: 2444; by computerized implementations of these algorithms, including, but not limited to: CLUSTAL in the PC/Gene program by Intelligenetics, Mountain View, Calif., GAP, BESTFIT, BLAST, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group (GCG), 7 Science Dr., Madison, Wis., USA; the CLUSTAL program is well described by Higgins and Sharp (1988) Gene 73: 237-244; Corpet et al. (1988) Nucleic Acids Research, 16:881-90; Huang, et al., Computer Applications in the Biosciences, 8:1-6, 1992; and Pearson, et al. (1994) Methods in Molecular Biology, 24:7-331. The BLAST family of programs which can be used for database similarity searches includes: BLASTN for nucleotide query sequences against nucleotide database sequences; BLASTX for nucleotide query sequences against protein database sequences; BLASTP for protein query sequences against protein database sequences; TBLASTN for protein query sequences against nucleotide database sequences; and TBLASTX for nucleotide query sequences against nucleotide database sequences. See, Current Protocols in Molecular Biology, Chapter 19, Ausubel, et al., Eds., Greene Publishing and Wiley-Interscience, New York, 1995. New versions of the above programs or new programs altogether will undoubtedly become available in the future, and can be used with the present invention.

[0367] Unless otherwise stated, sequence identity/similarity values provided herein refer to the value obtained using the BLAST 2.0 suite of programs, or their successors, using default parameters. Altschul et al. (1997) Nucleic Acids Res, 2:3389-3402. It is to be understood that default settings of these parameters can be readily changed as needed in the future.

[0368] As those ordinary skilled in the art will understand, BLAST searches assume that proteins can be modeled as random sequences. However, many real proteins comprise regions of nonrandom sequences which may be homopolymeric tracts, short-period repeats, or regions enriched in one or more amino acids. Such low-complexity regions may be aligned between unrelated proteins even though other regions of the protein are entirely dissimilar. A number of low-complexity filter programs can be employed to reduce such low-complexity alignments. For example, the SEG (Wooten and Federhen, (1993) Comput. Chem. 17:149-163) and XNU (Claverie and States (1993) Comput. Chem., 17:191-1) low-complexity filters can be employed alone or in combination.

[0369] "Sequence identity" or "identity" in the context of two nucleic acid or polypeptide sequences includes reference to the residues in the two sequences which are the same when aligned for maximum correspondence over a specified comparison window, and can take into consideration additions, deletions and substitutions. When percentage of sequence identity is used in reference to proteins it is recognized that residue positions which are not identical often differ by conservative amino acid substitutions, where amino acid residues are substituted for other amino acid residues with similar chemical properties (for example, charge or hydrophobicity) and therefore do not deleteriously change the functional properties of the molecule. Where sequences differ in conservative substitutions, the percent sequence identity may be adjusted upwards to correct for the conservative nature of the substitution. Sequences which differ by such conservative substitutions are said to have sequence similarity. Approaches for making this adjustment are well-known to those of skill in the art. Typically this involves scoring a conservative substitution as a partial rather than a full mismatch, thereby increasing the percentage sequence identity. Thus, for example, where an identical amino acid is given a score of 1 and a non-conservative substitution is given a score of zero, a conservative substitution is given a score between zero and 1. The scoring of conservative substitutions is calculated, for example, according to the algorithm of Meyers and Miller (1988) Computer Applic. Biol. Sci., 4: 11-17 for example, as implemented in the program PC/GENE (Intelligenetics, Mountain View, Calif., USA).

[0370] "Percentage of sequence identity" means the value determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the polynucleotide sequence in the comparison window may comprise additions, substitutions, or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions, substitutions, or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid base or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity.

[0371] The term "substantial identity" or "homologous" in their various grammatical forms in the context of polynucleotides means that a polynucleotide comprises a sequence that has a desired identity, for example, at least 60% identity, preferably at least 70% sequence identity, more preferably at least 80%, still more preferably at least 90% and even more preferably at least 95%, compared to a reference sequence using one of the alignment programs described using standard parameters. One of skill will recognize that these values can be appropriately adjusted to determine corresponding identity of proteins encoded by two nucleotide sequences by taking into account codon degeneracy, amino acid similarity, reading frame positioning and the like. Substantial identity of amino acid sequences for these purposes n normally means sequence identity of at least 60%, more preferably at least 70%, 80%, 90%, and even more preferably at least 95%.

[0372] Another indication that nucleotide sequences are substantially identical is if two molecules hybridize to each other under stringent conditions. However, nucleic acids which do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides which they encode are substantially identical. This may occur, for example, when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. One indication that two nucleic acid sequences are substantially identical is that the polypeptide which the first nucleic acid encodes is immunologically cross reactive with the polypeptide encoded by the second nucleic acid, although such cross-reactivity is not required for two polypeptides to be deemed substantially identical.

[0373] The term "substantial identity" or "homologous" in their various grammatical forms in the context of peptides indicates that a peptide comprises a sequence that has a desired identity, for example, at least 60% identity, preferably at least 70% sequence identity to a reference sequence, more preferably 80%, still more preferably 85%, even more preferably at least 90% or 95% sequence identity to the reference sequence over a specified comparison window. Preferably, optimal alignment is conducted using the homology alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol., 48:443. An indication that two peptide sequences are substantially identical is that one peptide is immunologically reactive with antibodies raised against the second peptide, although such cross-reactivity is not required for two polypeptides to be deemed substantially identical. Thus, a peptide is substantially identical to a second peptide, for example, where the two peptides differ only by a conservative substitution. Peptides which are "substantially similar" share sequences as noted above except that residue positions which are not identical may differ by conservative amino acid changes. Conservative substitutions typically include, but are not limited to, substitutions within the following groups: glycine and alanine; valine, isoleucine, and leucine; aspartic acid and glutamic acid; asparagine and glutamine; serine and threonine; lysine and arginine; and phenylalanine and tyrosine, and others as known to the skilled person.

[0374] "Biological subject" as used herein refers to a target biological object obtained, reached, or collected in vivo, ex-vivo, or in situ, that contains or is suspected of containing nucleic acids or polypeptides corresponding to a biomarker of Table 1.

[0375] "Biological sample" as used herein refers to a sample obtained from a biological subject, including sample of biological tissue or fluid origin, obtained, reached, or collected in vivo, ex-vivo, or in situ, that contains or is suspected of containing nucleic acids or polypeptides corresponding to a biomarker of Table 1. A biological sample also includes samples from a region of a biological subject containing precancerous or cancer cells or tissues. Such samples can be, but are not limited to, organs, tissues, fractions and cells isolated from mammals including, humans such as a patient. Biological samples also may include sections of the biological sample including tissues, for example, frozen sections taken for histologic purposes. A biological sample, as described herein, can be: a "control" or a "control sample" or a "test sample". A biological sample can be obtained from the uterus using commonly employed clinical practices (e.g., aspiration, brush, curettage, or hysteroscopy).

[0376] A "control" or "control value" refers to a representative of healthy, endometrial cancer-free biological subject or information obtained from a different individual or a normalized value, which can be based on baseline data obtained from a population or other acceptable sources. A control also can refer to a given level of a biomarker of Table 1, representative of the endometrial cancer-free population, that has been previously established based on measurements from normal, endometrial cancer-free individuals. A control also can be a reference data point in a database based on data obtained from control samples representative of a cancer-free population. Further, a control can be established by a specific age, sex, ethnicity or other demographic parameters. In some contexts, the control is implicit in the particular measurement. A control value or control can also refer to a "control score". Control scores can be values obtained from the determination of the expression level of one or more biomarkers of the invention. For example, different programs and algorithms are commercially available for generating formulas that yield a score value based on the measurement of the levels of one or more biomarkers, that can indicate whether an individual is likely to have a condition or not. In another example, a score over or below a certain threshold that may indicate an increased (or decreased) likelihood of having the disease. A control score value can be based on a single marker or a combination of markers.

[0377] A "control sample" refers to a sample of biological material representative of healthy, cancer-free animals or a normal biological subject obtained from a cancer-free population. The level of a biomarker of Table 1, in a control sample is desirably typical of the general population of normal, cancer-free animals of the same species. This sample either can be collected from an animal for the purpose of being used in the methods described in the present invention or it can be any biological material representative of normal, cancer-free animals suitable for use in the methods of this invention. A control sample also can be obtained from normal tissue from the animal that has cancer or is suspected of having cancer.

[0378] A "test sample" as used herein refers to a biological sample, including sample of biological tissue or fluid origin, obtained, reached, or collected in vivo, ex-vivo, or in situ, that contains or is suspected of containing nucleic acids or polypeptides corresponding to a biomarker of Table 1. A test sample also includes biological samples containing precancerous or cancer cells or tissues. A test sample also may include sections of the biological sample including tissues, for example, frozen sections taken for histologic purposes.

[0379] "Providing a biological subject, a biological sample, or a test sample" means to obtain a biological subject in vivo, ex-vivo, or in situ, including tissue or cell sample for use in the methods described in the present invention. Most often, this will be done by removing a sample of cells from an animal, but also can be accomplished in vivo, ex-vivo, or in situ, or by using previously isolated cells (for example, isolated from another person, at another time, and/or for another purpose). The sample can also be obtained from sources such as blood, serum, and uterine fluid.

[0380] "Data" includes, but is not limited to, information obtained that relates to "biological sample", "test sample", "control sample", and/or "control", as described above, wherein the information is applied in generating a test level for diagnostics, prevention, monitoring or therapeutic use. The present invention relates to methods for comparing and compiling data wherein the data is stored in electronic or paper formats. Electronic format can be selected from the group consisting of electronic mail, disk, compact disk (CD), digital versatile disk (DVD), memory card, memory chip, ROM or RAM, magnetic optical disk; tape, video, video clip, microfilm, internet, shared network, shared server and the like; wherein data is displayed, transmitted or analyzed via electronic transmission, video display, telecommunication, or by using any of the above stored formats; wherein data is compared and compiled at the site of sampling specimens or at a location where the data is transported following a process as: described above.

[0381] "Overexpression" of a gene or an "increased," or "elevated," level of a ribonucleotide or protein refers to a level of the gene, ribonucleotide or polypeptide that, in comparison with a control level/value of gene, ribonucleotides or polypeptide, is detectably higher. Comparison may be carried out by statistical analyses on numeric measurements of the expression; or, it may be done through visual examination of experimental results by qualified researchers. Examples of overexpression include a change of 10% or more, 20% or more 30% or more, 40% or more, or 50% or more in affected as compared to non-affected.

[0382] "Underexpression" of a gene or a "decreased," or "lower," level of a ribonucleotide or protein refers to a level of the gene, ribonucleotide or polypeptide that, in comparison with a control level of gene, ribonucleotides or polypeptide, is detectably lower. Comparison may be carried out by statistical analyses on numeric measurements of the expression; or, it may be done through visual examination of experimental results by qualified researchers. Examples of underexpression include a change of 10% or more, 20% or more 30% or more, 40% or more, or 50% or more in affected as compared to non-affected.

[0383] A level of ribonucleotide or polypeptide, that is "expected" in a control sample refers to a level that represents a typical, cancer-free sample, and from which an elevated, or diagnostic, presence of the polypeptide or polynucleotide, can be distinguished. Preferably, an "expected" level will be controlled for such factors as the age, sex, medical history, etc. of the mammal, as well as for the particular biological subject being tested.

[0384] The terms "isolated," "purified," or "biologically pure" refer to material that is free to varying degrees from components which normally accompany it as found in its native state. "Isolate" denotes a degree of separation from original source or surroundings. "Purify" denotes a degree of separation that is higher than isolation. A "purified" or "biologically pure" protein is sufficiently free of other materials such that any impurities do not materially affect the biological properties of the protein or cause other adverse consequences. That is, a nucleic acid or peptide of this invention is purified if it is substantially free of cellular material, viral material, or culture medium when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. Purity and homogeneity are typically determined using analytical chemistry techniques, for example, polyacrylamide gel electrophoresis or high performance liquid chromatography. The term "purified" can denote that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. For a protein that can be subjected to modifications, for example, phosphorylation or glycosylation, different modifications may give rise to different isolated proteins, which can be separately purified. Various levels of purity may be applied as needed according to this invention in the different methodologies set forth herein; the customary purity standards known in the art may be used if no standard is otherwise specified.

[0385] An "isolated nucleic acid molecule" can refer to a nucleic acid molecule, depending upon the circumstance, that is separated from the 5' and 3' coding sequences of genes or gene fragments contiguous in the naturally occurring genome of an organism. The term "isolated nucleic acid molecule" also includes nucleic acid molecules which are not naturally occurring, for example, nucleic acid molecules created-by recombinant DNA techniques.

[0386] "Nucleic acid" refers to deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or double-stranded form. The term encompasses nucleic acids containing known nucleotide analogs or modified backbone residues or linkages, which are synthetic, naturally occurring, and non-naturally occurring, which have similar binding properties as the reference nucleic acid, and which are metabolized in a manner similar to the reference nucleotides. Examples of such analogs include, without limitation, phosphorothioates, phosphoramidates, methyl phosphonates, chiral methyl phosphonates, 2-O-methyl ribonucleotides, and peptide-nucleic acids (PNAs).

[0387] Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively, modified variants thereof (for example, degenerate codon substitutions) and complementary sequences, as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with suitable mixed base and/or deoxyinosine residues (Batzer et al. (1991) Nucleic Acid Res, 19:081; Ohtsuka et al. (1985) J. Biol. Chem., 260:2600-2608; Rossolini et al. (1994) Mol. Cell Probes, 8:91-98). The term nucleic acid can be used interchangeably with gene, cDNA, mRNA, oligonucleotide, and polynucleotide.

[0388] A "label" or a "detectable moiety" is a composition that when linked with the nucleic acid or protein molecule of interest renders the latter detectable, via spectroscopic, photochemical, biochemical, immunochemical, or chemical means. For example, useful labels include radioactive isotopes, magnetic beads, metallic beads, colloidal particles, fluorescent dyes, electron-dense reagents, enzymes (for example, as commonly used in an ELISA), biotin, digoxigenin, or haptens. A "labeled nucleic acid or oligonucleotide probe" is one that is bound, either covalently, through a linker or a chemical bond, or noncovalently, through ionic bonds, van der Waals forces, electrostatic attractions, hydrophobic interactions, or hydrogen bonds, to a label such that the presence of the nucleic acid or probe may be detected by detecting the presence of the label bound to the nucleic acid or probe.

[0389] As used herein a "nucleic acid or oligonucleotide probe" is defined as a nucleic acid capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation. As used herein, a probe may include natural (i.e., A, G, C, or T) or modified bases (7-deazaguanosine, inosine, etc.). In addition, the bases in a probe may be joined by a linkage other than a phosphodiester bond, so long as it does not unduly interfere with hybridization. It will be understood by one of skill in the art that probes may bind target sequences lacking complete complementarity with the probe sequence depending upon the stringency of the hybridization conditions. The probes are preferably directly labeled with isotopes, for example, chromophores, lumiphores, chromogens, or indirectly labeled with biotin to which a streptavidin complex may later bind. By assaying for the presence or absence of the probe, one can detect the presence or absence of a target gene of interest.

[0390] The phrase "selectively (or specifically) hybridizes to" refers to the binding, duplexing, or hybridizing of a molecule only to a particular nucleotide sequence under stringent hybridization conditions when that sequence is present in a complex mixture (for example, total cellular or library DNA or RNA).

[0391] The phrase "stringent hybridization conditions" refers to conditions under which a probe will hybridize to its target complementary sequence, typically in a complex mixture of nucleic acids, but to no other sequences. Stringent conditions are sequence-dependent and circumstance-dependent; for example, longer sequences can hybridize with specificity at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen (1993) Techniques in Biochemistry and Molecular Biology-Hybridization with Nucleic Probes, "Overview of principles of hybridization and the strategy of nucleic acid assays". In the context of the present invention, as used herein, the term "hybridizes under stringent conditions" is intended to describe conditions for hybridization and washing under which nucleotide sequences at least 60% homologous to each other typically remain hybridized to each other. Preferably, the conditions are such that sequences at least about 65%, more preferably at least about 70%, and even more preferably at least about 75% or more homologous to each other typically remain hybridized to each other.

[0392] Generally, stringent conditions are selected to be about 5 to 10 C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. The Tm is the temperature (under defined ionic strength, pH, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30 C for short probes (for example, 10 to 50 nucleotides) and at least about 60 C for long probes (for example, greater than 50 nucleotides). Stringent conditions also may be achieved with the addition of destabilizing agents, for example, formamide. For selective or specific hybridization, a positive signal is at least two times background, preferably 10 times background hybridization.

[0393] Exemplary stringent hybridization conditions can be as following, for example: 50% formamide, 5.times.SSC and 1% SDS, incubating at 42 C, or 5.times.SSC and 1% SDS, incubating at 65 C., with wash in 0.2.times.SSC and 0.1% SDS at 65 C. Alternative conditions include, for example, conditions at least as stringent as hybridization at 68 C for 20 hours, followed by washing in 2.times.SSC, 0.1% SDS, twice for 30 minutes at 55 C and three times for 15 minutes at 60 C. Another alternative set of conditions is hybridization in 6.times.SSC at about 45 C, followed by one or more washes in 0.2.times.SSC, 0.1% SDS at 50-65 C. For PCR, a temperature of about 36 C is typical for low stringency amplification, although annealing temperatures may vary between about 32 C and 48 C depending on primer length. For high stringency PCR amplification, a temperature of about 62 C is typical, although high stringency annealing temperatures can range from about 50 C to about 65 C, depending on the primer length and specificity. Typical cycle conditions for both high and low stringency amplifications include a denaturation phase of 90 C to 95 C for 30 sec. to 2 min., an annealing phase lasting 30 sec. to 2 min., and an extension phase of about 72 C for 1 to 2 min.

[0394] Nucleic acids that do not hybridize to each other under stringent conditions can still be substantially identical if the polypeptides which they encode are substantially identical. This occurs, for example, when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. In such cases, the nucleic acids typically hybridize under moderately stringent hybridization conditions. Exemplary "moderately stringent hybridization conditions" include a hybridization in a buffer of 40% formamide, 1 M NaCl, 1% SDS at 37 C, and a wash in 1.times.SSC at 45 C. A positive hybridization is at least twice background. Those of ordinary skill will readily recognize that alternative hybridization and wash conditions can be utilized to provide conditions of similar stringency.

[0395] The term "target gene" or "target biomarker" or "target nucleic acid" or "target protein" can refer to a target nucleic acid (DNA and RNA) or protein (or polypeptide), (e.g., corresponding to the biomarkers in Table 1) and can include their polymorphic variants, alleles, mutants, and interspecies homologs that have (i) substantial nucleotide sequence homology (for example, at least 60% identity, preferably at least 70% sequence identity, more preferably at least 80%, still more preferably at least 90% and even more preferably at least 95%) with the nucleotide sequence indicated in ENSEMBL.TM. database for the indicated ID number; or (ii) at least 65% sequence homology with the amino acid sequence as indicated in the ENSEMBL.TM. record; or (iii) substantial nucleotide sequence homology (for example, at least 60% identity, preferably at least 70% sequence identity, more preferably at least 80%, still more preferably at least 90% and even more preferably at least 95%) with the nucleotide sequence as set forth in the ENSEMBL.TM. record with substantial sequence homology with the encoded amino acid sequence. As used in herein, and unless otherwise specified, these terms refer the entire gene sequence, mRNA sequence, and/or protein sequence as well as fragments of these sequences.

[0396] In a more specific definition, these terms refer to the minimal amount of nucleic acid or amino acid sequence that can be used to identify biomarker in a specific manner. The skilled artisan recognizes that the target genes/biomarker can have numerous splice forms and variants. When referring to a specific target gene or locus by a reference number (e.g., ENTREZ.TM. gene ID or ENSEMBL.TM.), all splices forms and variant which are included in the various embodiments of the invention. The target gene/biomarker can also comprise a regulatory element. These sequences are representative of one particular individual in the population of humans. Humans vary from one to another in their gene sequences. These variations are very minimal, sometimes occurring at a frequency of about 1 to 10 nucleotides per gene. Different forms of any particular gene exist within the human population. These different forms are called allelic variants. Allelic variants often do not change the amino acid sequence of the encoded protein; such variants are termed synonymous. Even if they do change the encoded amino acid (non-synonymous), the function of the protein is not typically affected. Such changes are evolutionarily or functionally neutral. When a gene ID (e.g., GENBANK.TM. or ENSEMBL.TM.) is referred to in the present application all allelic variants are intended to be encompassed by the term. The gene ID sequences given for a biomarker are provided merely as representative examples of a wild-type human sequence. The invention is not limited to a single allelic form of the amplified genes or regions (and proteins they encode).

EXAMPLES

[0397] The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques used by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

Example 1

Identification of Endometrial Cancer Biomarkers

[0398] In order to identify biomarkers for predicting and/or diagnosing endometrial cancer, gene expression levels from fifty-six endometrial primary tumors in several differentiation stages were compared with 10 normal (i.e., not having endometrial cancer) endometrial tissues by DNA microarray technique. This technique allows us to check the expression of the whole genome in a particular type of cell, tissue, organ, or in this case, check the differential gene expression between endometrial cancer and healthy endometrial tissue. A microarray chip contains small DNA sequences arranged in a regular pattern with specific addresses for probes for typically thousands of genes.

[0399] The amount of specific mRNAs in a sample can be estimated by it hybridization signal on the array.

[0400] Sample Description

[0401] Tumor samples were obtained from patients who underwent surgery and control tissue was obtained from non affected regions of endometrial tissue from the same patients. During preparation of the specimens, care was taken to macroscopically dissect the cancer away from any adjacent myometrium.

[0402] Ten control samples (nine of them were paired with their corresponding tumor samples and the tenth was an atrophic endometrium) were used and the basic characteristics of the other test samples are summarized in Table 3 below.

TABLE-US-00004 TABLE 3 Affected Samples used in Microarray studies Tumor FIGO Samples Sample Diagnosis Grade stage 1 Endometroid carcinoma G1 Ia 2 Endometroid carcinoma G1 Ib 3 Endometroid carcinoma G1 Ib 4 Endometroid carcinoma G1 Ib 5 Endometroid carcinoma G1 Ia 6 Endometroid carcinoma G1 Ia 7 Endometroid carcinoma G1 Ia 8 Endometroid carcinoma G2 Ib 9 Endometroid carcinoma G2 IIb 10 Endometroid carcinoma G2 IIIa 11 Endometroid carcinoma G2 Ib 12 Endometroid carcinoma G2 Ic 13 Endometroid carcinoma G2 Ia 14 Endometroid carcinoma G2 Ic 15 Endometroid carcinoma G2 Ic 16 Endometroid carcinoma G2 Ib 17 Endometroid carcinoma G2 IIb 18 Endometroid carcinoma G2 IIb 19 Endometroid carcinoma G2 Ib 20 Endometroid carcinoma G2 Ic 21 Endometroid carcinoma G2 IVb 22 Endometroid carcinoma G2 IIb 23 Endometroid carcinoma G2 Ic 24 Endometroid carcinoma G2 IIb 25 Endometroid carcinoma G2 Ib 26 Endometroid carcinoma G2 Ic 27 Endometroid carcinoma G2 Ib 28 Endometroid carcinoma G2 Ib 29 Endometroid carcinoma G2 IIb 30 Endometroid carcinoma G2 Ib 31 Endometroid carcinoma G3 Ic 32 Endometroid carcinoma G3 IIIa 33 Endometroid carcinoma G3 IIb 34 Endometroid carcinoma G3 IIb 35 Endometroid carcinoma G3 Ib 36 Endometroid carcinoma G3 IIa 37 Endometroid carcinoma G3 IIa 38 Endometroid carcinoma G3 Ic 40 ATIPIC HIPERPLASIA 41 ATIPIC HIPERPLASIA 42 ATIPIC HIPERPLASIA 43 Serous carcinoma G3 IIIc 44 Serous carcinoma G3 IIIc 45 Serous carcinoma G3 Ib 46 Serous carcinoma G3 Ib 47 Serous carcinoma G3 IIIa 48 Clara cell type G3 IIIc 49 Undifferenciated G3 IIb 50 Undifferenciated G3 IIIa 51 Villoglandular G3 Ib 52 Villoglandular G2 Ib 53 Adeno-squamous G2 Ib 54 Adeno-squamous G2 IIb 55 Adeno-squamous G3 Ic 56 Mucinous type G3 IIIa

[0403] Total RNA was extracted with the RNEASY.TM. mini kit (Qiagen, Hilden, Germany), following the instructions provided by the manufacturer. Quantity and quality of the obtained RNA was measured with a NANODROP.TM. (Nandrop ND-1000, Agilent 2100 Bioanalyzer) and low quality RNA was discarded from the array hybridization process.

[0404] Microarray Design

[0405] Microarrays for Gene Expression were designed by the Tethys algorithm using the ENSEMBL.TM. database. For sequences where we did not find high quality probes, we complemented the design with Oryzon Optimized Agilent probes. DNA microarray synthesis was outsourced to Agilent.

[0406] The Whole Genome Gene Expression Array contains: [0407] 20148 Oryzon High Quality probes from ENSEMBL.TM. Database. [0408] 5698 Oryzon Tm optimized Agilent probes.

[0409] The total number of probes was 25846.

aRNA labeling

[0410] Cy3 and Cy5 labeled aRNA was produced using the MESSAGEAMPLIFICATION.TM. kit by Ambion (Ref: 1819 for 96.times. kit or Ref: 1751 for 20.times. kit). These kits are used with some modifications introduced by Oryzon genomics. RNA labeling was performed essentially using the Eberwine protocol (Van Gelder, 1992) commercialized by Ambion with the MESSAGEAMPLIFICATION.TM. Kit (Ambion/Applied Biosystems) with minor modifications. 500 ng of total RNA was reverse transcribed in presence of oligo(dT).sub.24, second-strand synthesis was generated and transcription of this dsDNA was prepared using CTP_Cy3 or CTP_Cy5 (PERKINELMER.TM.). Amplified cRNA was quantified by Nanodrop ND-1000 and cRNA quality was controlled with the Agilent RNA Bionalyzer 2100.

[0411] Microarray Hybridization

[0412] Microarray hybridization was performed at 60.degree. C. and 17 hours hybridization time according to Agilent indications, using Agilent gaskets (G2534-60002), Agilent hybridization chambers (G2534A) and in an Agilent DNA Hybridization Oven (G2545A). Oryzon hybridization controls are also used in hybridization process. Controls for the hybridization process corresponding to 3 cDNA clones of maize (Xet, Zm42, Exp) were included in all analysis. Exp is used as the negative spike control and was not amplified nor labeled. For Xet and Zm42 PCR fragments were generated by PCR amplification from the vector with universal primers and cRNA was generated using in vitro transcription systems (T7 or T3 MEGASCRIPT.TM. kit; Ambion) with CTP_Cy3 or CTP_Cy5 (PERKINELMER.TM.). Both of the positive spike controls Xet and Zm42 were with both the Cy5 and Cy3 fluorofor.

[0413] Data Acquisition

[0414] Initial Raw Data were obtained using an Agilent DNA Microarray Scanner (G2505B) and Agilent acquisition software (Feature Extraction Software). The extraction protocol performed does not use background subtraction, computation of dye biases and ratio correction.

[0415] Data Analysis

[0416] A large number of controls were included in the microarray designs to monitor scanner and array performance and to control spatial homogeneity and correct deviations. This way, the overall error on the microarray data measurements can be estimated by the spreading analysis of the data from the controls.

[0417] The mean fold change or M values can be ranked based on their probability of being different from 0, according to the absolute value of the regularized t-statistic (Baldi and Long, 2001) which uses a Bayesian framework to derive a modified and improved t-student statistics. To make Fold Change based selection, the mean M distribution was used. This distribution is adjusted to a normal distribution and an iterative process is used to define the mean M numbers that are outside the distribution. The cut-off is chosen as n times the Standard deviations (a) from the mean. This method generates a robust mean and standard deviation and allows to dynamically adjusting the cut-off value to the noise distribution of the data. Typically, values with mean FC>3.sigma. or mean FC<-3.sigma. of the sample data distribution were selected.

[0418] An indirect analysis comparison where the expression levels of particular biomarkers in tumor samples were compared to a reference RNA pool obtained from a group of over 20 cell lines (melanoma, lung cancer, ovarian cancer, colon cancer, and several non-cancer cell lines). The expression level of particular genes in the normal samples (controls) were compared to the same reference pool and final expression fold changes between tumor and normal endometrial tissue were generated in silico eliminating the reference pool.

[0419] Candidate genes were selected as biomarkers for endometrial cancer based on fold overexpression, p-value, and other factors. Table 1 in the Detailed Description of the Invention shows 17 overexpressed genes and 3 genes underexpresssed identified using these procedures. The overexpression of these genes was validated by RT-PCR as described in the next examples.

[0420] The results from the microarray studies are summarized in Table 1 in the Detailed Description of the Invention, which shows the common abbreviation used for the gene, the ENSEMBL.TM. gene, transcript and protein accession numbers along with the fold overexpression and calculated p-values.

Example 2

Uterine Fluid Sample Preparation

[0421] Endometrial aspirates were collected with the help of a CORNIER.TM. pipelle, after complete informed consent was obtained from all patients. The aspirate (uterine fluid) was immediately transferred to an EPPENDORF.TM. tube containing 500 microliters of a RNA preserving solution (RNALATER.TM., Ambion). The sample was centrifuged and the pellet containing a representative population of cells from the uterine cavity was further processed for RNA extraction (Qiagen). Quality tests (Bioanalyzer) were performed before the analysis of gene expression by TAQMAN.TM. technology for the selected markers of endometrial carcinoma.

Example 3

Correlation of Biomarkers in Primary Tumor and in Uterine Fluid

[0422] The levels of biomarkers from primary tumor sample and uterine fluid sample obtained by the procedure of Example 2 were compared as by RT-PCR following the general RT-PCR protocol as described in Example 4. The biomarkers in this study included ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN whose expression level was found to be surprisingly correlated between the primary tumor and endometrial aspirates (uterine fluid). See FIG. 1. As can be seen in FIG. 1, the expression level of a number of biomarkers of endometrial cancer are correlated in uterine fluid and primary tumor. In particular, it was found that there was a high level of correlation of expression of biomarkers corresponding to ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN in tumor sample and in samples obtained from uterine fluid. Thus, the inventors have surprisingly finding of a group of genes that can be used to diagnosis or predict an increased likelihood of endometrial cancer based on their expression levels in samples obtained from uterine fluid. Furthermore, the inventors have shown that uterine fluid can be used to assess biomarkers for endometrial cancer. For example, prognostic biomarkers for endometrial cancer, biomarkers for staging endometrial cancer, biomarkers for determining the type of endometrial cancer (e.g., Type 1 vs. Type II) or type (endometrioid, clear cell, serrous, etc.), auxiliary diagnostic biomarkers, differential diagnosis biomarkers, can be assayed in uterine fluid to characterize the cancer.

Example 4

Confirmation of Overexpression of Biomarkers by Quantitative RT-PCR

[0423] Once array data were obtained, a group of upregulated and downregulated genes in tumor samples compared with normal tissue were selected in-part based on their p-values and standard deviations. These candidates were selected to determine their expression levels by an independent technique using a different set of tumor samples.

[0424] Microfluidic Cards (MFC) from Applied Biosystems were used to perform RT-PCR with RNA isolated from tumor and normal endometrial tissue samples. In this case both types of tissues, healthy and carcinogenic were obtained from the same patient by microdissection procedures. These studies confirmed the microarray results for most of the markers of Table 1. Another set of RT-PCT studies were performed using aspirates obtained from endometrial cancer patients (confirmed) and aspirates from non-affected individuals. These studies using aspirates samples are described in more detail below.

[0425] Aspirate samples were obtained following a procedure similar to that described in Example 2. The description of patient characteristics for the affected and non-affected samples are given in Table 4 and Table 5 below.

[0426] Briefly, wells of the Microfluidic Card contain Applied Biosystems fluorogenic 5' nuclease assays that detect the real-time amplification of the array selected targets. Relative levels of gene expression are determined from the fluorescence data generated during PCR using the ABI PRISM.RTM. 7900HT Sequence Detection System (7900HT SDS) Relative Quantification software.

[0427] Data analysis was made using the comparative .DELTA..DELTA.Ct method of relative quantification. Differentially expressed genes were confirmed by thorough statistical analysis using a modified T-test.

[0428] The samples used for the study described in this Example included:

[0429] Samples from 30 patients having endometrial cancer: 25 endometroid adenocarcinomas with 9 in G3, 9 in G2 and 7 in G1. And 5 tumor samples from different type II carcinomas (4 in G3 and 1 in G2)

[0430] Samples from 24 patients not having endometrial cancer ("controls" or "normals"). These were a heterogeneous mix of samples some of them from patients with other non-tumoral pathologies liked polyps: 4 samples from patients with atrophic endometriod, 4 normal samples, two from patients having polyps from post-menopausical women and 11 samples from pre-menopausical women (7 of them in secretory phase and 4 in proliferative phase of the cycle). See Tables below for a summary of samples.

TABLE-US-00005 TABLE 4 Affected Samples for RT-PCR Studies Aspirates from Tumor FIGO women with a tumor Sample Diagnosis Grade stage 1 Endometroid carcinoma G1 IIb 2 Endometroid carcinoma G1 Ia 3 Endometroid carcinoma G1 Ib 4 Endometroid carcinoma G1 Ib 5 Endometroid carcinoma G1 Ia 6 Endometroid carcinoma G1 Ia 7 Endometroid carcinoma G1 Ib 8 Endometroid carcinoma G2 IIb 9 Endometroid carcinoma G2 Ib 10 Endometroid carcinoma G2 Ib 11 Endometroid carcinoma G2 Ib 12 Endometroid carcinoma G2 Ib 13 Endometroid carcinoma G2 Ia 14 Endometroid carcinoma G2 Ia 15 Endometroid carcinoma G2 Ib 16 Endometroid carcinoma G2 Ib 17 Endometroid carcinoma G3 IIb 18 Endometroid carcinoma G3 Ic 19 Endometroid carcinoma G3 Ic 20 Endometroid carcinoma G3 Ib 21 Endometroid carcinoma G3 Ic 22 Endometroid carcinoma G3 Ib 23 Endometroid carcinoma G3 Ib 24 Endometroid carcinoma G3 Ib 25 Endometroid carcinoma G3 Ic 26 Clara Cell type G3 IIb 27 Clara Cell type G3 IIIc 28 Adeno-squamous G3 IIIa 29 Undifferenciated G3 IIIc 30 squamo-transitional G2 Ib

TABLE-US-00006 TABLE 5 Non-Affected Samples for RT-PCR Studies Control aspirates 7 pre-menopausic in secretory phase 6 pre-menopausic in proliferative phase 11 aspirates from postmenopausical women

[0431] Experimental Procedures

[0432] RNA samples were isolated from aspirate samples following the procedure above described and a quality control was performed previously to final sample selection. Aspirate samples were collected as described in Example 2.

[0433] RT-PCR was performed following Applied Biosystem standard protocol for the 7900HT system. The protocol consisted in a two-step method where the first step is the generation of cDNA from the RNA samples using a High Capacity cDNA Kit and the second step is the amplification of cDNA, once loaded in the MFC, by the ABI PRISM.RTM. 7900 HT system.

[0434] RT-PCR data were collected for a set of 20 genes identified in Example 1 and quantified relative to POLR2A levels. The RQ values for the aspirates corresponding to the 30 tumor samples and the 24 samples that were not endometrial cancer (normals) are illustrated in a box and whiskers plot, see FIGS. 2A and 2B. Table 2 in the Detailed Description of the Invention gives a summary of the mean RQ values, standard error of the mean and p-values calculated for these markers in this sample set. As can be seen, the p-values obtained using the control sample set in the microarray studies (Table 1) were significantly improved in a different sample set using different techniques (microarray versus RT-PCR) and different sources of sample (aspirates versus primary tumor). In most cases the p-value improved over 100-fold for the biomarkers. This is related in part to the robust nature of the microarray experimental design and robust selection of markers based on the Inventors' criteria.

[0435] The next table shows the sensitivity and specificity for each individual gene on the patent application and the area under de ROC (AUROC) curve for each gene when comparing the RQ values from the 30 tumour samples and the 24 control samples. A support vector machine (SVM) program was used to calculate the data. As can be seen in the table below, the markers identified in these studies have excellent sensitivity and/or specificity for predicting an increased likelihood and/or diagnosis of endometrial cancer. Furthermore, the AUROC values for these biomarkers indicate that these markers are very useful for diagnosis of endometrial cancer.

TABLE-US-00007 TABLE 6 Sensitivity, Specificity and AUROC values for the biomarkers of the invention determined from aspirates samples in affected (endometrial cancer) and non-affected individuals. GENE sensitivity specificity AUROC ACAA1 66.67% 90.00% 0.81 AP1M2 58.33% 86.67% 0.83 CGN 79.17% 76.67% 0.81 DDR1 79.17% 90.00% 0.89 EPS8L2 70.83% 86.67% 0.81 FASTKD1 70.83% 76.67% 0.84 GMIP 75.00% 83.33% 0.88 IKBKE 83.33% 73.33% 0.90 P2RX4 62.50% 96.67% 0.82 P4HB 91.67% 96.67% 0.97 PHKG2 70.83% 93.33% 0.84 PPFIBP2 58.33% 96.67% 0.78 PPP1R16A 75.00% 80.00% 0.85 RASSF7 100.00% 60.00% 0.89 RNF183 95.83% 73.33% 0.88 SIRT6 79.17% 73.33% 0.84 TJP3 79.17% 76.67% 0.82 EFEMP2 66.67% 83.33% 0.88 SOCS2 79.17% 93.33% 0.93 DCN 66.67% 90.00% 0.85

[0436] Control samples were a heterogeneous group with pre and post-menopausical women. At the same time, aspirates from pre-menopausical women could be divided in two categories depending of the uterine endometrial cycle phase they were when the sample was taken: proliferative or secretory. The characterization of secretory versus proliferative phase patients was accomplished by a pathologist using standard techniques.

[0437] Some of the genes tested could give a false positive result for endometrial cancer if the aspirate was taken from pre-menopausical women in secretory phase. In order to check which genes could give false positives depending of the cycle phase or which others could distinguish between tumour samples and secretory phase, we performed a statistical analysis comparing tumours with different control groups. [0438] tumors versus control samples (all the control samples: 24 samples) [0439] tumors versus control samples minus the ones in secretory phase: 17 samples [0440] tumors samples versus control samples in secretory phase: 7 samples [0441] tumors samples versus control samples from postmenopausal women: 11 samples

[0442] The area ROC for each comparison was calculated using the GraphPad Prism program and anova test was applied to see if the differences among these groups were significant.

[0443] In the Tables below the following abbreviations are used for p-values:

*** p<0.0001 ** p<0.001 *p<0.01 ns (not significant).

[0444] As it is shown on the tables there are genes, like P4HB or SOCS2, which separate the tumour samples from the control independently of the nature of the control samples (post-menopausical, pre-menopausical in secretory or in proliferative). Other genes like P2RX4 or PPFIBP2, could distinguish between a tumour sample (affected) and a sample in secretory phase better as compared to controls from postmenopausal women.

[0445] This observation opens the possibility of using different algorithms and/or different set of genes depending if the test is interrogating pre-menopausical or post-menopausical women. Furthermore, a primary modality for screening for endometrial problems is the trans-vaginal ultrasound which is used to estimate endometrial thickness where patients having a thicker endometrium (over a certain threshold) are likely to have endometrial cancer or another disease or condition. Endometrium thickness also varies as a function of the phase of the menstrual with individuals in secretory phase having a thicker endometrium as compared to individuals in proliferative phase. Thus, these finding indicate that the methods and biomarkers of the invention can be used to aid and improve the ability of transvaginal ultrasound to identify endometrial cancer.

TABLE-US-00008 TABLE 7 Summary of Data for RT-PCR Studies comparing the expression levels of biomarkers in aspirates (30) from patients affected with endometrial cancer and aspirates obtained from individuals all patients non affected with endometrial cancer (24). Comparison por 30T/24Crtl ROC 30Tvs24Ctrl Anova P4HB 0.974 *** SOCS2 0.955 *** IKBKE 0.897 *** RNF183 0.883 *** EFEMP2 0.881 *** PHKG2 0.875 *** DCN 0.854 *** PPP1R16A 0.846 *** AP1M2 0.843 *** FASTKD1 0.838 *** SIRT6 0.836 *** CGN 0.829 *** GMIP 0.824 *** TJP3 0.824 *** RASSF7 0.817 *** ACAA1 0.817 *** EPS8L2 0.813 *** P2RX4 0.807 *** DDR1 0.769 ** PPFIBP2 0.745 *

[0446] Table 7 shows that the 20 biomarkers capable of distinguishing aspirates from endometrial cancer affected patients from aspirate from all control non-affected patients with high ROC values and/or excellent statistical significance.

TABLE-US-00009 TABLE 8 Summary of Data for RT-PCR Studies comparing the expression levels of biomarkers in aspirates (30) from patients affected with endometrial cancer and aspirates obtained from individuals patients non-affected with endometrial cancer and that were not in secretory phase (17) comparison 30T/17 Ctrl ROC 30T vs 17Ctrl Anova P4HB 0.963 *** SOCS2 0.936 *** RNF183 0.904 *** EFEMP2 0.900 *** FASTKD1 0.863 *** AP1M2 0.859 *** IKBKE 0.858 *** PHKG2 0.845 *** CGN 0.832 *** SIRT6 0.828 ** PPP1R16A 0.817 ** DCN 0.801 ** TJP3 0.8 ** GMIP 0.798 *** RASSF7 0.798 ** ACAA1 0.784 ** EPS8L2 0.767 ** P2RX4 0.728 * DDR1 0.680 ns PPFIBP2 0.644 ns

[0447] Table 8 shows the rankings of 20 biomarkers of the invention capable of distinguishing aspirates from endometrial cancer affected patients from aspirates from all control non-affected patients excluding patients in the secretory phase. Table 7 shows the biomarkers of the invention have high ROC values and/or excellent statistical significance for separating these populations.

TABLE-US-00010 TABLE 9 Summary of Data for RT-PCR studies comparing the expression levels of biomarkers in aspirates (30) from patients affected with endometrial cancer and aspirates obtained from individuals patients non affected with endometrial cancer and that were in secretory phase (7) comparison 30T/7 Sec ROC 30T vs 7 Sec Anova P4HB 1 ** SOCS2 1.000 *** P2RX4 1 *** IKBKE 0.991 *** PPFIBP2 0.991 ** DDR1 0.986 ** DCN 0.981 ** PHKG2 0.948 ** EPS8L2 0.924 * PPP1R16A 0.917 ** GMIP 0.9 * ACAA1 0.895 * TJP3 0.881 * RASSF7 0.864 * SIRT6 0.857 * EFEMP2 0.833 ns RNF183 0.831 ns CGN 0.82 ns AP1M2 0.805 ns FASTKD1 0.779 ns

[0448] As can be seen in the Table 9 preferred markers capable of distinguishing aspirates from endometrial cancer affected patients from aspirates from non-endometrial cancer affected patients in secretory phase include P4HB, SOCS2 P2RX4, IKBKE, PPFIB2, DDR1 and DCN which have high ROC values and/or excellent statistical significance.

[0449] As seen from the data in Tables 7 & 9 above examples of genes capable of differentiating between aspirates from patients having tumor and aspirates from all non-affected patients (including secretory phase) and/or between aspirates from patients having tumor and aspirates from non-affected patients in secretory phase include P4HB, SOCS2, and IKBKE which have high statistical significance and ROC values.

TABLE-US-00011 TABLE 10 Summary of Data for RT-PCR Studies comparing the expression levels of biomarkers in aspirates (30) from patients affected with endometrial cancer and aspirates obtained from post-menopausal patients non affected with endometrial cancer (11). Ranking por 30T/11N ROC 30Tvs11crtl postm Anova PHKG2 0.9476 * P4HB 0.9424 *** EFEMP2 0.903 *** RNF183 0.8909 *** SOCS2 0.8667 * FASTKD1 0.8439 ** GMIP 0.8394 ** SIRT6 0.8364 ** AP1M2 0.8182 * IKBKE 0.7955 ns CGN 0.7864 * PPP1R16A 0.7652 ns TJP3 0.7515 ns RASSF7 0.7515 ns ACAA1 0.7242 ns DCN 0.7167 ns EPS8L2 0.697 ns P2RX4 0.6303 ns DDR1 0.5879 ns PPFIBP2 0.5318 ns

[0450] As can be seen in the Table 10 preferred markers capable of distinguishing aspirates from endometrial cancer affected patients from aspirate from post menopausal non endometrial cancer affected patients include PHKG2, P4HB, EFEMP2, RNF183, and SOCS2 which have high ROC values and/or excellent statistical significance.

[0451] In reference to FIGS. 2A and 2B (box and whisker plot), RQ: relative quantity, it is the relative amount of RNA for a specific gene present on the tumours samples referred to the amount present on the control sample for the same gene.

[0452] To calculate the RQ the Ct values of each gene were normalise respect to the Ct of the endogenous gene to get the delta Ct. The formula 2.sup.-(deltaCt) was used to calculate de RQ.

[0453] A number of endogenous genes can be used as a control for normalization as well as other controls for normalization. In one example a preferred endogenous gene has the following characteristics: it is a gene constitutively expressed in the same tissue under different circumstances like for example cancer development. So it could be used to normalize differences in the amount of cDNA when loading the samples or variations due to experimental reasons for the qRT-PCR.

[0454] We have tested four different housekeeping genes as possible endogenous genes for normalization purposes: 18S, B2M, PFN-1 and POLR2A. Finally, POLR2A was the most stable gene from all of them and all the calculations and statistics were done using it as endogenous. Its expression level is similar to the genes questioned in our test and different as compared to 18 S whose expression is quiet high compared to the genes selected for the test. It is contemplated that endogenous biomarkers such as POLR2A, B2M, PFN1, HMBS, G6PD, or PABPN1 or another stable gene can be used for normalization purposes in the methods of the invention if they so require.

Example 5

Profiles for Diagnosing Endometrial Cancer

[0455] A support vector machine based algorithm was used to identify combinations of markers of Table 1 that are useful for predicting endometrial cancer and/or an increased likelihood of having endometrial cancer. In particular, the publically available program DTREG program was used to analyze the data (see the www at DTREG.COM).

[0456] Support vector machine algorithm can be used for many applications including identifying gene expression profiles for separating populations having different phenotypic characteristics. The idea behind the algorithm is a multidimensional representation of the data, e.g., each marker is plotted on a different dimension and a plane is sought though this multidimensional representation of the data that can separate the phenotypes. The plan through the "middle" is referred to as the separating hyperplane and represents a solution: answers (e.g., expression level over a given threshold value) that fall on one side of the line fall into one category (e.g., cancer) and answers (e.g., expression level over a given threshold value) that follow on the other side of the line correspond to the other category (e.g., no cancer). A number of separating hyper plane can be possible for each dataset. The question becomes which is the best separating hyperplane. In support vector machine theory, the best solution is referred to as the maximum margin hyperplane. This maximum margin hyperplane is the one that separates the two groups and adopts the maximal distance from any one of the given expression profiles.

[0457] Although individual genes show a high sensitivity and specificity, these parameters are even higher when combined several genes. Some examples of the sensitivity, specificity and AUROC genes combined two to two, three to three, four to four, five to five, six to six, seven to seven and all of them together. See the Table below for a summary of the data.

TABLE-US-00012 TABLE 11 Data Summarizing Predictive Values for Combinations combinations sensitivity specificity AUROC IKBKE + P4HB 91.67% 100.00% 0.978 IKBKE + SOCS2 79.17% 96.67% 0.951 P4HB + SOCS2 91.67% 100.00% 1 GMIP + IKBKE 79.17% 90.00% 0.915 GMIP + P4HB 95.83% 96.67% 0.982 GMIP + SOCS2 100.00% 86.67% 0.999 GMIP + SOCS2 + IKBKE 95.83% 100.00% 1 GMIP + SOCS2 + P4HB 91.67% 100.00% 0.983 GMIP + IKBKE + P4HB 91.67% 100.00% 0.978 IKBKE + P4HB + SOCS2 91.67% 100.00% 0.981 GMIP + IKBKE + P4HB + SOCS2 100.00% 100.00% 1 GMIP + SOCS2 + IKBKE + EPS8L2 91.67% 100.00% 0.993 GMIP + SOCS2 + P4HB + EPS8L2 91.67% 100.00% 0.976 GMIP + IKBKE + P4HB + EPS8L2 91.67% 100.00% 0.976 IKBKE + P4HB + SOCS2 + EPS8L2 87.50% 100.00% 0.981 GMIP + IKBKE + P4HB + SOCS2 + DDR1 91.67% 100.00% 1 GMIP + IKBKE + P4HB + SOCS2 + EPS8L2 + PPP1R16A 91.67% 100.00% 0.999 GMIP + IKBKE + P4HB + SOCS2 + PHKG2 + RASSF7 95.83% 100.00% 1 GMIP + IKBKE + P4HB + SOCS2 + DDR1 + EPS8L2 95.83% 100.00% 1 GMIP + IKBKE + P4HB + SOCS2 + EPS8L2 + PPP1R16A + DDR1 95.83% 100.00% 1 DDR1 + EPS8L2 + GMIP + IKBKE + P2RX4 + P4HB + 100.00% 100.00% 1 PHKG2 + PPP1R16A + RASSF7 + SIRT6 + TJP3 + SOCS2 DDR1 + EPS8L2 + GMIP + IKBKE + P2RX4 + P4HB + 100.00% 100.00% 1 PHKG2 + PPP1R16A + RASSF7 + SIRT6 + TJP3 + SOCS2 + RNF183 ALL TOGETHER: 20 GENES 100.00% 100.00% 1

[0458] As can be seen in the Table above very high sensitivity and specificities were obtained for combinations of the biomarkers of the invention and the AUROC values are very high. Thus, these results show that combinations of 2 or more markers chosen from ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2, and DCN give unexpectedly good sensitivity and specificity for predicting an increased likelihood and/or diagnosing endometrial cancer. These results were obtained from samples from uterine fluid and indicate that combinations of biomarkers detected in uterine fluid can be useful for diagnosing and/or characterizing endometrial cancer. Furthermore, these results were obtained in samples from pre and post menopausal women and therefore represents a set of markers that can be examined across these types of patients. It is noted that different programs and algorithms can be used to generate profiles or fingerprint patterns. The invention is intended to encompass profiles and/or fingerprint patterns using programs and algorithms other than DTREG as used herein. The profiles identified in Table 11 are non-limiting examples used to illustrate that combinations of the biomarkers of Table 1 have excellent sensitivity and specificity for endometrial cancer.

[0459] Additional Combinations

[0460] The values of sensitivity and specificity although fully define the validity of a diagnostic test have the disadvantage of not providing relevant information when making a clinical decision to a particular test result. However, they have the advantage of been intrinsic properties to the test and define its validity irrespective of the prevalence of the disease in the population to which it applies.

[0461] Sensitivity

[0462] It is the probability of classifying correctly an individual patient or the probability that a individual with cancer obtains a positive result when applying the diagnostic test

[0463] Specificity

[0464] It is the probability of classifying correctly a healthy individual or the probability that a healthy individual obtaining a negative result when applying the diagnostic test Sensitivity and specificity can, therefore, to assess the validity of a diagnostic test. However, these concepts are not much help in clinical practice. When a patient undergoes a diagnostic test, the doctor has no a priori information about their diagnosis so the question arises to the next one: given a positive (or negative) on the test? What is the probability that the individual tested has the disease (or not)? These probabilities are known as positive predictive value and negative predictive value of a particular test. Positive predictive value is the probability of having the disease if the individual has a positive result when applying the diagnostic test. Negative predictive value is the probability that an individual who has obtained a negative result on the test, is actually healthy.

[0465] Clinicians prefer diagnostic tests with high negative predictive value as they can not allow people with cancer get a wrong diagnosis. For this reason we have prioritized these combinations which give us the highest negative predictive values.

[0466] The follow values in Table 12 were calculated using the indicated markers as determined by RT-PCR in uterine fluid samples.

TABLE-US-00013 TABLE 12 DTREG-SVM combinations sensitivity specificity AUROC NPV PPV P4HB + SOCS2 91.67% 100.00% 1 93.75% 100.00% GMIP + IKBKE + P4HB + SOCS2 100.00% 100.00% 1 100.00% 100.00% GMIP + IKBKE + P4HB + SOCS2 + FASTKD1 100.00% 100.00% 1 100.00% 100.00% GMIP + IKBKE + P4HB + SOCS2 + DDR1 95.83% 100.00% 1 96.77% 100.00% GMIP + IKBKE + P4HB + SOCS2 + PHKG2 91.67% 100.00% 1 93.75% 100.00% GMIP + IKBKE + P4HB + SOCS2 + SIRT6 91.67% 100.00% 1 93.75% 100.00% GMIP + IKBKE + P4HB + SOCS2 + ACAA1 100.00% 100.00% 1 100.00% 100.00% GMIP + IKBKE + P4HB + SOCS2 + AP1M2 91.67% 96.67% 0.979 93.55% 95.65% GMIP + IKBKE + P4HB + SOCS2 + EFEMP2 91.67% 100.00% 1 93.75% 100.00% GMIP + IKBKE + P4HB + SOCS2 + EPS8L2 91.67% 100.00% 1 93.75% 100.00% GMIP + IKBKE + P4HB + SOCS2 + P2RX4 83.33% 96.67% 0.964 87.88% 95.24% GMIP + IKBKE + P4HB + SOCS2 + PPFIBP2 91.67% 96.67% 0.979 93.55% 95.65% GMIP + IKBKE + P4HB + SOCS2 + PPP1R16A 95.83% 100.00% 1 96.77% 100.00% GMIP + IKBKE + P4HB + SOCS2 + ACAA1 + FASTKD1 100.00% 100.00% 1 100.00% 100.00% GMIP + IKBKE + P4HB + SOCS2 + FASTKD1 + PHKG2 100.00% 100.00% 1 100.00% 100.00% GMIP + IKBKE + P4HB + SOCS2 + FASTKD1 + SIRT6 100.00% 100.00% 1 100.00% 100.00% ACAA1 + AP1M2 + EPS8L2 + IKBKE + P2RX4 + P4HB + 100.00% 100.00% 1 100.00% 100.00% PPFIBP2 + PPP1R16A + SIRT6 + EFEMP2 GMIP + IKBKE + P4HB + EFEMP2 100.00% 93.33% 0.999 100.00% 92.31% DDR1 + FASTKD1 + GMIP + IKBKE + P4HB + PHKG2 + 100.00% 100.00% 1 100.00% 100.00% SIRT6 + EFEMP2 + SOCS2 DDR1 + FASTKD1 + GMIP + IKBKE + P4HB + PHKG2 + 100.00% 100.00% 1 100.00% 100.00% SIRT6 + EFEMP2 P4HB + EFEMP2 + IKBKE + GMIP + FASTKD1 100.00% 100.00% 1 100.00% 100.00%

[0467] The combinations shown in FIG. 18 (P4HB, EFEMP2, SIRT6, DDR1, GMIP, and FASTKD1) and FIG. 19 (P4HB, EFEMP2, SIRT6, PHKG2, GMIP, and FASTKD1), and the combination of all 20 markers have sensitivities, specificities, NPVs, and PPVs of 100% and AUROCs of 1.

[0468] Maximizing Negative Predictive Value: New samples: three new cancer samples and 24 no tumor samples giving a total amount of samples in the following analysis (33T and 48 non tumor) with the additional sample having the following characteristics:

TABLE-US-00014 Aspirates from Tumor FIGO women with a tumor Sample Diagnosis Grade stage 31 Endometroid carcinoma G1 IA 32 Endometroid carcinoma G2 IB 33 Endometroid/ G3 IA squamo-transitional

TABLE-US-00015 Control aspirates 4 pre-menopausic in secretory phase 5 pre-menopausic in proliferative phase 4 pre-menopausic (unknown cycle phase) 11 aspirates from postmenopausical women

[0469] The calculated the risk of cancer for 48 non tumor and 33 tumor samples using the following combination of genes ACAA1, AP1M2, EPS8L2, IKBKE, P2RX4, P4HB, PPFIBP2, PPP1R16A, SIRT6, and EFEMP2 the result is shown in FIG. 17.

[0470] FIG. 18 shows the calculated risk of cancer for the 48 non-tumor and 33 tumor samples using FASTKD1, GMIP, P4HB, EFEMP2, DDR1, and SIRT6.

[0471] FIG. 19 shows the calculated risk of cancer for the 48 non-tumor and 33 tumor samples using FASTKD1, GMIP, P4HB, EFEMP2, PHKG2, and SIRT6.

[0472] As shown on FIG. 17, the first combination is able to classify all the samples correctly but the percentage of some healthy samples of having cancer are very close to 50%: some cancer samples are too close to be misclassified when using this combination. In summary, the risk of misclassifying cancer patients with a false diagnosis. Although the combinations in FIG. 18 and FIG. 19 misclassify one and two healthy patients samples respectively, both of them classify correctly all the cancer patients and they do it with a higher percentage of risk of cancer than the previous combination. For that reason these combinations are valuable from a clinical point of view.

Example 6

Detection of Protein Corresponding to the Biomarkers of Table 1

[0473] Detection of protein corresponding to the Biomarkers of Table 1 can be accomplished by any number of means available to the skill artisan. According to this method samples from controls (or a control value is established) and affected individuals are obtained (e.g., serum, tissue, and uterine fluid) and probe for with antibodies selective or specific to the particular biomarker. One method for detecting the proteins is by western blot analysis and is exemplified as in the case of P4HB.

[0474] Western blot analysis from human samples from normal endometrial tissue and tumour endometrial cancer tissues in order to test the protein level of P4HB (aprox. 60 kDa) in these samples.

[0475] Gels were loaded with 40 ug of total protein extracts from each sample. As can be seen in FIG. 10, tumor samples stained much more strongly for P4HB as compared to normal tissue.

[0476] The samples tested include four normal tissues (N) and four tumour tissues (T). Normal and tumours tissues were obtained from the same patient. As a positive control: total protein extract from the endometrial tumour cell line Isikawa. The Antibody used: LS-C38385 from LifeSpan.

[0477] The results confirm to protein level the results obtained in the array and the TaqMan experiments.

[0478] Western blot analysis was performed for AP1M2, IKBKE, EPS8L2, DDR1, CGN, and TJP3. See FIG. 10 through FIG. 16. These results confirm at the protein level the results obtained in the array and the TAQMAN.TM. experiments for these biomarkers.

[0479] For immunohistochemistry validation, tissue microarrays were constructed. In order to cover the complete range from normal tissue to different types and grades of endometrial carcinomas, representative areas from 70 paraffin-embedded carcinomas (56 endometrioid, 6 serous papillary, 1 mucinous, 4 clear cell carcinomas, 3 carcinosarcomas), and 11 non-neoplastic endometria (4 atrophic, 3 proliferative, 1 secretory endometrial and 3 hyperplasias), were carefully selected and marked on individual paraffin blocks. Two tissue cores of 1 mm in diameter were obtained from each paraffin block and were precisely arrayed in a new paraffin block. Sections of 5 .mu.m were obtained from all tissue microarray paraffin blocks. The protocol was approved by the Institutional Review Board at Hospital Vall D'Hebron, and informed consent was obtained from all of the patients. P4HB, PPP1R16A and EPS8L2 were detected by the indirect immunoperoxidase assay with citrate buffer pH 7.3 for antigen retrieval. Sections were incubated with a primary antibodies against P4HB (LS-C38385) and PPP1R16A (H00084988-M06) for 1 h at room temperature using a dilution 1:500 and 1:100, respectively, and EPS8L2 (H00064787-B01) overnight at 1:100 dilution. Thereafter sections were incubated with peroxidase conjugated goat anti-mouse immunoglobulin (EnVision Dual System, DAKO, Glostrup, Denmark). Endogenous peroxidase activity was quenched with 3% H2O2. Sections were washed, and reactions were developed with diaminobenzidine, followed by counterstaining with haematoxylin. Semiquantitative evaluation of the proteins was performed by three independent investigators, scoring the intensity of the stained and the percentage of positive cells.

[0480] TMA immunohistochemistry confirmed the differential expression of the three proteins at the tumoral glands when compared to the normal endometrial glands. P4HB, PPP1R16A and EPS8L2 presented a specific cytoplasmatic expression within the tumoral cells in all carcinoma histological types and grades, and an absence or faint cytoplasmatic stain within the normal epithelial glands. These results confirm at the protein level the results obtained for these proteins in the microarray and quantitative PCR experiments described herein.

Example 7

ACAA1

[0481] ACAA1 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that ACAA1 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue and it was surprisingly found that ACAA1 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the methods described in Examples 2-4. Example 5 shows that ACAA1 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0482] The sequence of an mRNA corresponding to ACAA1 is given in ENSEMBL accession no. ENST00000333167 and has a sequence as in SEQ ID NO:1

TABLE-US-00016 1 ATGTGGTTCTGCGCGTGTGCGGACGGCTGTCTGTTAACTCCGCGGTCAGTTCCCGGACTG 61 GTGGCTGGTCTGCAGGGTTGACCTGCGCAATGCAGAGGCTGCAGGTAGTGCTGGGCCACC 121 TGAGGGGTCCGGCCGATTCCGGCTGGATGCCGCAGGCCGCGCCTTGCCTGAGCGGTGCCC 181 CGCAGGCCTCGGCCGCGGACGTGGTGGTGGTGCACGGGCGGCGCACGGCCATCTGCCGGG 241 CGGGCCGCGGCGGCTTCAAGGACACCACCCCCGACGAGCTTCTCTCGGCAGTCATGACCG 301 CGGTTCTCAAGGACGTGAATCTGAGGCCGGAACAGCTGGGGGACATCTGTGTCGGAAATG 361 TGCTGCAGCCTGGGGCCGGGGCAATCATGGCCCGAATCGCCCAGTTTCTGAGTGACATCC 421 CGGAGACTGTGCCTTTGTCCACTGTCAATAGACAGTGTTCGTCGGGGCTACAGGCAGTGG 481 CCAGCATAGCAGGTGGCATCAGAAATGGGTCTTATGACATTGGCATGGCCTGTGGGGTGG 541 AGTCCATGTCCCTGGCTGACAGAGGGAACCCTGGAAATATTACTTCGCGCTTGATGGAGA 601 AGGAGAAGGCCAGAGATTGCCTGATTCCTATGGGGATAACCTCTGAGAATGTGGCTGAGC 661 GGTTTGGCATTTCACGGGAGAAGCAGGATACCTTTGCCCTGGCTTCCCAGCAGAAGGCAG 721 CAAGAGCCCAGAGCAAGGGCTGTTTCCAAGCTGAGATTGTGCCTGTGACCACCACGGTCC 781 ATGATGACAAGGGCACCAAGAGGAGCATCACTGTGACCCAGGATGAGGGTATCCGCCCCA 841 GCACCACCATGGAGGGCCTGGCCAAACTGAAGCCTGCCTTCAAGAAAGATGGTTCTACCA 901 CAGCTGGAAACTCTAGCCAGGTGAGTGATGGGGCAGCTGCCATCCTGCTGGCCCGGAGGT 961 CCAAGGCAGAAGAGTTGGGCCTTCCCATCCTTGGGGTCCTGAGGTCTTATGCAGTGGTTG 1021 GGGTCCCACCTGACATCATGGGCATTGGACCTGCCTATGCCATCCCAGTAGCTTTGCAAA 1081 AAGCAGGGCTGACAGTGAGTGACGTGGACATCTTCGAGATCAATGAGGCCTTTGCAAGCC 1141 AGGCTGCCTACTGTGTGGAGAAGCTACGACTCCCCCCTGAGAAGGTGAACCCCCTGGGGG 1201 GTGCAGTGGCCTTAGGGCACCCACTGGGCTGCACTGGGGCACGACAGGTCATCACGCTGC 1261 TCAATGAGCTGAAGCGCCGTGGGAAGAGGGCATACGGAGTGGTGTCCATGTGCATCGGGA 1321 CTGGAATGGGAGCCGCTGCCGTCTTTGAATACCCTGGGAACTGAGTGAGGTCCCAGGCTG 1381 GAGGCGCTACGCAGACAGTCCTGCTGCTCTAGCAGCAAGGCAGTAACACCACAAAAGCAA 1441 AACCACATGGGAAAACTCAGCACTGGTGGTGGTGGCAGTGGACAGATCAAGGCACTTCAA 1501 CTCATTTGGAAAATGTGAACACTGATGACATGGTATAGGAGTGGGTGGGGTGTTGAGCCA 1561 CCCATCAGACCCTCTTTAGCTGTGCAAGATAAAAGCAGCCTGGGTCACCCAGGCCACAAG 1621 GCCATGGTTAATTCTTAAGGCAAGGCAAATCCATGGATGAGAAGTGCAATGGGCATAGTA 1681 AAAGTGCATGAATTT

[0483] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000333664 and has a sequence as in SEQ ID NO:2

TABLE-US-00017 1 MQRLQVVLGHLRGPADSGWMPQAAPCLSGAPQASAADVVVVHGRRTAICRAGRGGFKDTT 61 PDELLSAVMTAVLKDVNLRPEQLGDICVGNVLQPGAGAIMARIAQFLSDIPETVPLSTVN 121 RQCSSGLQAVASIAGGIRNGSYDIGMACGVESMSLADRGNPGNITSRLMEKEKARDCLIP 181 MGITSENVAERFGISREKQDTFALASQQKAARAQSKGCFQAEIVPVTTTVHDDKGTKRSI 241 TVTQDEGIRPSTTMEGLAKLKPAFKKDGSTTAGNSSQVSDGAAAILLARRSKAEELGLPI 301 LGVLRSYAVVGVPPDIMGIGPAYAIPVALQKAGLTVSDVDIFEINEAFASQAAYCVEKLR 361 LPPEKVNPLGGAVALGHPLGCTGARQVITLLNELKRRGKRAYGVVSMCIGTGMGAAAVFE 421 YPGN

[0484] Primers for amplifying the sequence ACAA1 can be designed using primer design software such as Oligo Calc and/or Primer 3.

[0485] Examples of primer pairs for amplifying ACAA1 include those in

TABLE-US-00018 Forward SEQ ID NO: 3 GAGCTTCTCTCGGCAGTCAT Reverse SEQ ID NO: 4 CTCAGAAACTGGGCGATTC Forward SEQ ID NO: 5 GCAATCATGGCCCGAATC Reverse SEQ ID NO: 6 CCCCGACGAACACTGTCTAT Forward SEQ ID NO: 7 GTGCCTTTGTCCACTGTCAA Reverse SEQ ID NO: 8 ACAGGCCATGCCAATGTC Forward SEQ ID NO: 9 TCACGGGAGAAGCAGGATAC Reverse SEQ ID NO: 10 CTCTTGGTGCCCTTGTCATC Forward SEQ ID NO: 11 GGCTGACAGTGAGTGACGTG Reverse SEQ ID NO: 12 AGGGGGTTCACCTTCTCAG Forward SEQ ID NO: 13 GTGGCATCAGAAATGGGTCT Reverse SEQ ID NO: 14 CTCTGGCCTTCTCCTTCTCC Forward SEQ ID NO: 15 ATTACTTCGCGCTTGATGGA Reverse SEQ ID NO: 16 AGGGCAAAGGTATCCTGCTT Forward SEQ ID NO: 17 GCCTGCCTTCAAGAAAGATG Reverse SEQ ID NO: 18 TAAGACCTCAGGACCCCAAG Forward SEQ ID NO: 19 TGGGGTCCTGAGGTCTTATG Reverse SEQ ID NO: 20 TCTCGAAGATGTCCACGTCA Forward SEQ ID NO: 21 GTGGCATCAGAAATGGGTCT Reverse SEQ ID NO: 22 AGGGCAAAGGTATCCTGCTT Forward SEQ ID NO: 23 TGACCCAGGATGAGGGTATC Reverse SEQ ID NO: 24 TCTCGAAGATGTCCACGTCA Forward SEQ ID NO: 25 GGAGACTGTGCCTTTGTCCA Reverse SEQ ID NO: 26 CTCTGTCAGCCAGGGACAT

[0486] Probes for detecting ACAA1 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

TABLE-US-00019 SEQ ID NO: 27 CGGTTCTCAAGGACGTGAAT SEQ ID NO: 28 AGTGACATCCCGGAGACTGT SEQ ID NO: 29 GTGGCATCAGAAATGGGTCT SEQ ID NO: 30 AGCTGAGATTGTGCCTGTGA SEQ ID NO: 31 ATCAATGAGGCCTTTGCAAG SEQ ID NO: 32 ACAGAGGGAACCCTGGAAAT SEQ ID NO: 33 GATTGCCTGATTCCTATGGG SEQ ID NO: 34 GTCCAAGGCAGAAGAGTTGG SEQ ID NO: 35 ATGCCATCCCAGTAGCTTTG SEQ ID NO: 36 GCCTGTGGGATAACCTCTGA SEQ ID NO: 37 AAACTGAAGCCTGCCTTCAA SEQ ID NO: 38 ATAGACAGTGTTCGTCGGGG

[0487] A probe for detecting a ACAA1 nucleic acid that was used on the microarray has a sequence as in

TABLE-US-00020 SEQ ID NO: 39 GCTACGCAGACAGTCCTGCTGCTCTAGCAGCAAGGCAGTAACACCACAAA AGCAAAACCA

[0488] Other probes to ACAA1 are known in the art and/or can be readily designed by the skilled artisan.

[0489] Antibodies against ACAA1 include, but are not limited to, Rabbit polyclonal anti-ACAA1 Cat# HPA006764 from atlas antibodies (just recognizes the first transcript); and Mouse polyclonal antibody raised against a full-length human ACAA1 protein. Catalog #: H00000030-B01 from abnova (MaxPab).

Example 8

AP1M2

[0490] AP1M2 (adaptor-related protein complex 1, mu 2 subunit) also known as D9Ertd818e, HSMU1B, MU-1B, MU1B) was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that AP1M2 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue and it was surprisingly found that AP1M2 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Examples 2-4. Example 5 shows that AP1M2 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0491] AP1M2 is a subunit of the heterotetrameric clathrin adaptor-related protein complex 1 (AP-1), that play pivotal roles in many vesicle trafficking pathways within the cell. This protein is capable of interacting with tyrosine-based sorting signals. AP1 is expressed exclusively in epithelial cells. All AP complexes comprise two large subunits of 100-130 kDa (.alpha. and .beta.1 in AP1), a medium subunit of 50 kDa (.mu.1 in AP1), and a small subunit of 17-20 kDa (.sigma.1 in AP1). PMID: 10338135

[0492] In clathrin-coated vesicles, AP-2 is located between the lipid bilayer and clathrin lattice, and presumably is anchoring clathrin to membrane. AP1M2 is member of the adaptor medium chain family termed Mu1B, which is specifically expressed in polarized epithelial cells and some exocrine cells. Mu1B is most closely related to the ubiquitously-expressed Mu1A subunit of AP-1 (79% identity at the amino acid level).

[0493] The sequence of an mRNA corresponding to AP1M2 is given in ENSEMBL accession number ENST00000250244 and has a sequence as in SEQ ID NO:40

TABLE-US-00021 GGCGCTTCCGCAGGAAGAAGGAAGCGGCGCCGCCATCGCCTCCCGGCGCT CCCTCCCCGACTCCTAAGTCCTTCGGCCGCCACCATGTCCGCCTCGGCTG TCTTCATTCTGGACGTTAAGGGCAAGCCATTGATCAGCCGCAACTACAAG GGCGATGTGGCCATGAGCAAGATTGAGCACTTCATGCCTTTGCTGGTACA GCGGGAGGAGGAAGGCGCCCTGGCCCCGCTGCTGAGCCACGGCCAGGTCC ACTTCCTATGGATCAAACACAGCAACCTCTACTTGGTGGCCACCACATCG AAGAATGCCAATGCCTCCCTGGTGTACTCCTTCCTGTATAAGACAATAGA GGTATTCTGCGAATACTTCAAGGAGCTGGAGGAGGAGAGCATCCGGGACA ACTTTGTCATCGTCTACGAGTTGCTGGACGAGCTCATGGACTTTGGCTTC CCGCAGACCACCGACAGCAAGATCCTGCAGGAGTACATCACTCAGCAGAG CAACAAGCTGGAGACGGGCAAGTCACGGGTGCCACCCACTGTCACCAACG CTGTGTCCTGGCGCTCCGAGGGTATCAAGTATAAGAAGAACGAGGTCTTC ATTGATGTCATAGAGTCTGTCAACCTGCTGGTCAATGCCAACGGCAGCGT CCTTCTGAGCGAAATCGTCGGTACCATCAAGCTCAAGGTGTTTCTGTCAG GAATGCCAGAGCTGCGGCTGGGCCTCAATGACCGCGTGCTCTTCGAGCTC ACTGGCCGCAGCAAGAACAAATCAGTAGAGCTGGAGGATGTAAAATTCCA CCAGTGCGTGCGGCTCTCTCGCTTTGACAACGACCGCACCATCTCCTTCA TCCCGCCTGATGGTGACTTTGAGCTCATGTCATACCGCCTCAGCACCCAG GTCAAGCCACTGATCTGGATTGAGTCTGTCATTGAGAAGTTCTCCCACAG CCGCGTGGAGATCATGGTCAAGGCCAAGGGGCAGTTTAAGAAACAGTCAG TGGCCAACGGTGTGGAGATATCTGTGCCTGTACCCAGCGATGCCGACTCC CCCAGATTCAAGACCAGTGTGGGCAGCGCCAAGTATGTGCCGGAGAGAAA CGTCGTGATTTGGAGTATTAAGTCTTTCCCGGGGGGCAAGGAGTACTTGA TGCGAGCCCACTTTGGCCTCCCCAGTGTGGAAAAGGAAGAGGTGGAGGGC CGGCCCCCCATCGGGGTCAAGTTTGAGATCCCCTACTTCACCGTCTCTGG GATCCAGGTCCGATACATGAAGATCATTGAGAAAAGTGGTTACCAGGCCC TGCCCTGGGTTCGCTACATCACCCAGAGTGGCGATTACCAACTTCGTACC AGCTAGAAGGGAGAAGAGATGGGGGCTTGAACACGGGGCTTCCTTACAGC CCCGGATGCAGATTTTAGAGGGAGGGCAGGTGCGGGCTGTGTGTGTCTGT GTGAGGGCAGGTCCTGGACTTGGCAGTTTCTTGCTCCCAGCACCCGCCCC TTCCTCACCTCTTCCTTATTCCATAGGCTGGGAGAGAAACTCTCTGCTTC CCTCGCCCTTGGAGCTTTCCCCATCCCCCTGATTTTATATGAAGAAATAG AAGAGGGGCTTGAAGTCCCCCTCGCGAGTGCCTTCTTGCAATTACCTGCC TTAGCGGGTGTTGCGGGTCCCTCCTTCACAGCCGCTGAGCCCAGAGGTCC CGCTGGCCCCTCCTCTGAATTTTAGGATGTCATTAAAAAGATGAATCTA

[0494] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000250244 and has a sequence as in SEQ ID NO:41

TABLE-US-00022 MSASAVFILDVKGKPLISRNYKGDVAMSKIEHFMPLLVQREEEGALAPLL SHGQVHFLWIKHSNLYLVATTSKNANASLVYSFLYKTIEVFCEYFKELEE ESIRDNFVIVYELLDELMDFGFPQTTDSKILQEYITQQSNKLETGKSRVP PTVTNAVSWRSEGIKYKKNEVFIDVIESVNLLVNANGSVLLSEIVGTIKL KVFLSGMPELRLGLNDRVLFELTGRSKNKSVELEDVKFHQCVRLSRFDND RTISFIPPDGDFELMSYRLSTQVKPLIWIESVIEKFSHSRVEIMVKAKGQ FKKQSVANGVEISVPVPSDADSPRFKTSVGSAKYVPERNVVIWSIKSFPG GKEYLMRAHFGLPSVEKEEVEGRPPIGVKFEIPYFTVSGIQVRYMKIIEK SGYQALPWVRYITQSGDYQLRTS

[0495] Primers for amplifying the sequence ENST00000250244 can be designed using primer design software such as Oligo Calc.

[0496] Examples of primer pairs for amplifying AP1M2 include:

TABLE-US-00023 Forward SEQ ID NO: 42 CGCCACCATGTCCGCCTCGGCTG Reverse SEQ ID NO: 43 GCTCAATCTTGCTCATGGCCAC (Ex2) Forward SEQ ID NO: 44 CAGGTCCACTTCCTATGGATC (ex 2) Reverse SEQ ID NO: 45 CAAAGTTGTCCCGGATGCTC (Ex4) Forward SEQ ID NO: 46 CGCTCCGAGGGTATCAAG (EX5) Reverse SEQ ID NO: 47 CTTGCTGCGGCCAGTGAGC (ex6-7) Forward SEQ ID NO: 48 GACTTTGAGCTCATGTCATACC (Ex7) Reverse SEQ ID NO: 49 CTTAATACTCCAAATCACGACG (Ex9) Forward SEQ ID NO: 50 GTTTGAGATCCCCTACTTC (Ex10) Reverse SEQ ID NO: 51 GCCTGGTAACCACTTTTCTCAATG (Ex11) Forward SEQ ID NO: 52 CTGGGTTCGCTACATCACC (Ex11) Reverse SEQ ID NO: 53 GCCCCGTGTTCAAGC (Ex12) Forward SEQ ID NO: 54 CATGCCTTTGCTGGTACAG (Ex2) Reverse SEQ ID NO: 55 GAGTACACCAGGGAGGCATTG (Ex3) Forward SEQ ID NO: 56 CTCCCTGGTGTACTCCTTC (Ex3) Reverse SEQ ID NO: 57 GCTGTCGGTGGTCTGCGGGAA G (Ex4) Forward SEQ ID NO: 58 CAGCAAGATCCTGCAGGAG (Ex4-5) Reverse SEQ ID NO: 59 CAGGTTGACAGACTCTATG (Ex5)

[0497] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0498] Probes for detecting AP1M2 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Examples of probes include:

TABLE-US-00024 SEQ ID NO: 60 ATGAAGAAATAGAAGAGGGGCTTGAAGTCCTCCTCGCGAGTGCCTTCTT GCAATTACCTG SEQ ID NO: 61 CCAGGTCCACTTCCTATGGATCAAACACAGCAACCTCTACTTGGTGGCCA CCACATCG SEQ ID NO: 62 GACAATAGAGGTATTCTGCGAATACTTCAAGGAGCTGGAGGAG SEQ ID NO: 63 CAATGACCGCGTGCTCTTCGAGCTCACTGGCCGCAGCAAGAACAAATCA GTAGA SEQ ID NO: 64 TTTCCCGGGGGGCAAGGAGTACTTGATGCGAGCCCACTTTGGCCTCCCC AGTGTGG

[0499] Other probes to AP1M2 are known in the art and/or can be readily designed by the skilled artisan.

[0500] Antibodies against AP1M2 include, but are not limited to, Proteintech Group, Inc. Cat#10618-1-AP which is an affinity purified rabbit polyclonal antibody with an antigen which was a recombinant AP1M2 protein that included the amino acids 1-320 of the protein and from Abnova Cat# H00010053-B01, which is a mouse polyclonal antibody against the full length protein.

Example 9

CGN

[0501] CGN (also known as DKFZp779N1112, FLJ39281, and KIAA1319) was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that CGN was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue and it was surprisingly found that CGN was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Examples 2-4. Example 5 shows that CGN can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0502] The sequence of an mRNA corresponding to CGN is given in ENSEMBL accession number ENST00000271636 and has a sequence as in SEQ ID NO:65

TABLE-US-00025 ENSG00000143375: gene, just one transcript ENST00000271636 GAGGGAGCTCCGAGGACGAGGGGGAGGGCCGGAGCTGCGCGTGCTGCTT TGCCCGAGCCCGAGCCCGAGCCCGAGCCCGAGCCCGAGCCCGAGCCCGA ACGCAAGCCTGGGAGCGCGGAGCCCGGCTAGGGACTCCTCCTATTTATG GAGCAGGCACCCAACATGGCTGAGCCCCGGGGCCCCGTAGACCATGGAG TCCAGATTCGCTTCATCACAGAGCCAGTGAGTGGTGCAGAGATGGGCAC TCTACGTCGAGGTGGACGACGCCCAGCTAAGGATGCAAGAGCCAGTACC TACGGGGTTGCTGTGCGTGTGCAGGGAATCGCTGGGCAGCCCTTTGTGG TGCTCAACAGTGGGGAGAAAGGCGGTGACTCCTTTGGGGTCCAAATCAA GGGGGCCAATGACCAAGGGGCCTCAGGAGCTCTGAGCTCAGATTTGGAA CTCCCTGAGAACCCCTACTCTCAGGTCAAGGGATTTCCTGCCCCCTCGC AGAGCAGCACATCTGATGAGGAGCCTGGGGCCTACTGGAATGGAAAGCT ACTCCGTTCCCACTCCCAGGCCTCACTGGCAGGCCCTGGCCCAGTGGAT CCTAGTAACAGAAGCAACAGCATGCTGGAGCTAGCCCCGAAAGTGGCTT CCCCAGGTAGCACCATTGACACTGCTCCCCTGTCTTCAGTGGACTCACT CATCAACAAGTTTGACAGTCAACTTGGAGGCCAGGCCCGGGGTCGGACT GGCCGCCGAACACGGATGCTACCCCCTGAACAGCGCAAACGGAGCAAGA GCCTGGACAGCCGCCTCCCACGGGACACCTTTGAGGAACGGGAGCGCCA GTCCACCAACCACTGGACCTCTAGCACAAAATATGACAACCATGTGGGC ACTTCGAAGCAGCCAGCCCAGAGCCAGAACCTGAGTCCTCTCAGTGGCT TTAGCCGTTCTCGTCAGACTCAGGACTGGGTCCTTCAGAGTTTTGAGGA GCCGCGGAGGAGTGCACAGGACCCCACCATGCTGCAGTTCAAATCAACT CCAGACCTCCTTCGAGACCAGCAGGAGGCAGCCCCACCAGGCAGTGTGG ACCATATGAAGGCCACCATCTATGGCATCCTGAGGGAGGGAAGCTCAGA AAGTGAAACCTCTGTGAGGAGGAAGGTTAGTTTGGTGCTGGAGAAGATG CAGCCTCTAGTGATGGTTTCTTCTGGTTCTACTAAGGCCGTGGCAGGGC AGGGTGAGCTTACCCGAAAAGTGGAGGAGCTACAGCGAAAGCTGGATGA AGAGGTGAAGAAGCGGCAGAAGCTAGAGCCATCCCAAGTTGGGCTGGAG CGGCAGCTGGAGGAGAAAACAGAAGAGTGCAGCCGACTGCAGGAGCTGC TGGAGAGGAGGAAGGGGGAGGCCCAGCAGAGCAACAAGGAGCTCCAGAA CATGAAGCGCCTCTTGGACCAGGGTGAAGATTTACGACATGGGCTGGAG ACCCAGGTGATGGAGCTGCAGAACAAGCTGAAACATGTCCAGGGTCCTG AGCCTGCTAAGGAGGTGTTACTGAAGGACCTGTTAGAGACCCGGGAACT TCTGGAAGAGGTCTTGGAGGGGAAACAGCGAGTAGAGGAGCAGCTGAGG CTGCGGGAGCGGGAGTTGACAGCCCTGAAGGGGGCCCTGAAAGAGGAGG TAGCCTCCCGTGACCAGGAGGTGGAACATGTCCGGCAGCAGTACCAGCG AGACACAGAGCAGCTCCGCAGGAGCATGCAAGATGCAACCCAGGACCAT GCAGTGCTGGAGGCCGAGAGGCAGAAGATGTCAGCCCTTGTGCGAGGGC TGCAGAGGGAGCTGGAGGAGACTTCAGAGGAGACAGGGCATTGGCAGAG TATGTTCCAGAAGAACAAGGAGGATCTTAGAGCCACCAAGCAGGAACTC CTGCAGCTGCGAATGGAGAAGGAGGAGATGGAAGAGGAGCTTGGAGAGA AGATAGAGGTCTTGCAGAGGGAATTAGAGCAGGCCCGAGCTAGTGCTGG AGATACTCGCCAGGTTGAGGTGCTCAAGAAGGAGCTGCTCCGGACACAG GAGGAGCTTAAGGAACTGCAGGCAGAACGGCAGAGCCAGGAGGTGGCTG GGCGACACCGGGACCGGGAGTTGGAGAAGCAGCTGGCGGTCCTGAGGGT CGAGGCTGATCGAGGTCGGGAGCTGGAAGAACAGAACCTCCAGCTACAA AAGACCCTCCAGCAACTGCGACAGGACTGTGAAGAGGCTTCCAAGGCTA AGATGGTGGCCGAGGCAGAGGCAACAGTGCTGGGGCAGCGGCGGGCCGC AGTGGAGACGACGCTTCGGGAGACCCAGGAGGAAAATGACGAATTCCGC CGGCGCATCCTGGGTTTGGAGCAGCAGCTGAAGGAGACTCGAGGTCTGG TGGATGGTGGGGAAGCGGTGGAGGCACGACTACGGGACAAGCTGCAGCG GCTGGAGGCAGAGAAACAGCAGCTGGAGGAGGCCCTGAATGCGTCCCAG GAAGAGGAGGGGAGTCTGGCAGCAGCCAAGCGGGCACTGGAGGCACGCC TAGAGGAGGCTCAGCGGGGGCTGGCCCGCCTGGGGCAGGAGCAGCAGAC ACTGAACCGGGCCCTGGAGGAGGAAGGGAAGCAGCGGGAGGTGCTCCGG CGAGGCAAGGCTGAGCTGGAGGAGCAGAAGCGTTTGCTGGACAGGACTG TGGACCGACTGAACAAGGAGTTGGAGAAGATCGGGGAGGACTCTAAGCA AGCCCTGCAGCAGCTCCAGGCCCAGCTGGAGGATTATAAGGAAAAGGCC CGGCGGGAGGTGGCAGATGCCCAGCGCCAGGCCAAGGATTGGGCCAGTG AGGCTGAGAAGACCTCTGGAGGACTGAGCCGACTTCAGGATGAGATCCA GAGGCTGCGGCAGGCCCTGCAGGCATCCCAGGCTGAGCGGGACACAGCC CGGCTGGACAAAGAGCTACTGGCCCAGCGACTGCAGGGGCTGGAGCAAG AGGCAGAGAACAAGAAGCGTTCCCAGGACGACAGGGCCCGGCAGCTGAA GGGTCTCGAGGAAAAAGTCTCACGGCTGGAAACAGAGTTAGATGAGGAG AAGAACACCGTGGAGCTGCTAACAGATCGGGTGAATCGTGGCCGGGACC AGGTGGATCAGCTGAGGACAGAGCTCATGCAGGAAAGGTCTGCTCGGCA GGACCTGGAGTGTGACAAAATCTCCTTGGAGAGACAGAACAAGGACCTG AAGACCCGGTTGGCCAGCTCAGAAGGCTTCCAGAAGCCTAGTGCCAGCC TCTCTCAGCTTGAGTCCCAGAATCAGTTGTTGCAGGAGCGGCTACAGGC TGAAGAGAGGGAGAAGACAGTTCTGCAGTCTACCAATCGAAAACTGGAG CGGAAAGTTAAAGAACTATCCATCCAGATTGAAGACGAGCGGCAGCATG TCAATGACCAGAAAGACCAGCTAAGCCTGAGGGTGAAGGCTTTGAAGCG TCAGGTGGATGAAGCAGAAGAGGAAATTGAGCGACTGGACGGCCTGAGG AAGAAGGCCCAGCGTGAGGTGGAGGAGCAGCATGAGGTCAATGAACAG CTCCAGGCCCGGATCAAGTCTCTGGAGAAGGACTCCTGGCGCAAAGCTT CCCGCTCAGCTGCTGAGTCAGCTCTCAAAAACGAAGGGCTGAGCTCAGA TGAGGAATTCGACAGTGTCTACGATCCCTCGTCCATTGCATCACTGCTT ACGGAGAGCAACCTACAGACCAGCTCCTGTTAGCTCGTGGTCCTCAAGG ACTCAGAAACCAGGCTCGAGGCCTATCCCAGCAAGTGCTGCTCTGCTCT GCCCACCCTGGGTTCTGCATTCCTATGGGTGACCCAATTATTCAGACCT AAGACAGGGAGGGGTCAGAGTGATGGTGATAAAAAAAAAAAATCATCAG CAATAAGCTGATAGATGGACTTTCCACTGTAGGAGTGGACATTTCAAGC CAACTGAGCCTTTTCCTCAAGTGCCGACACCTCCCTCATCTCTCTTATA GTGGAAGGATGGTCAGCATTAGGCTGATGGGGACTGAGAAGGATAGGAA GGGATAGAAATTGCCATGTGTATAAAGCTTTATTCTTTAGCCCTTAACC CTAAGGCTCAGGGAAATACCCTATGTTATTGTGCTCCCTGGATTCCTGC AACTCATTTTCCTTCCACTCTGGAGCAGGGTGAGGGGAATGTTATGGGT AACAGACATGCAGGCATGGCTCTACCCATTTCTTTGCACAAGTATGGGG CCCATGTGGTAGTCCCCATACCCCTCCAGTTCCTATATTTTTGTCTTCT TCCTTTCCCCTCTTTGCCATTCCTACCTTGCATTTTTCCTGTCAGTGCC TTAGCCAAGGCAAGGAGATAAGGATGCTCTTCTTGCTTTTTATATCTGC ACATTCATACCTCTCCAAAGACCAGCTTTTCCCCAGCCAGGGCCCTCAG CCTTCCCTGCTGCCCCAGTGATTGATTGAGAGAGCTGTTGGGGTTTCTC TGCCAATGACCCCTGGGAGAGGGACTTTGGTAGGGTCATGATAAAGTGG CGGGGGTCTGGTCCTGCTCAGGGTTTTCATCCTTCCTCCTCTCCCTCCT CTGTGACTGTGGATATGGTTATAAGGTGGTTGCACCTGGGAGCCCTGAC AACTGGCTGCACAAATTCCAAAAGTAAAGGTGTCAGTCCCTGTGGCCTT CCTTGGGGCTTCTCTGACCACATGTGCCCAACTTCAATAAGAGAACCAA GGGACCCTCATTTTCTGAGGTGCTTGGCTCTGATTCAGGGCTTTGCAAG GGGTTAGAAGCTGACTGTAAAAATGGGAAGAGGCAACGGAAGACATTTA TTTCTCCTTTGGATTTTGGGGAGAACCAAGCCCTGGTAGGGAAGAGGTA AGGGGGATGATTCACCTCCATATTTCCTAAGCAGGTTGTATAGGGAGCC GGTGGCAGGAGGAAGGCTGTTTTCACAAATGACTTGTAATGTCGTGATT AAAAAAATTCCTATATTCTTCTGCAAATCAAACGTTCTTTCCCAATCCA ATCCAGCCTTGGTTTTATTTTAAATTAAATATTAAAATTACACATTTAT ATTGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

[0503] The start and stop codons are indicated in bold.

[0504] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000271636 and has a sequence as in SEQ ID NO:66

TABLE-US-00026 MEQAPNMAEPRGPVDHGVQIRFITEPVSGAEMGTLRRGGRRPAKDARAS TYGVAVRVQGIAGQPFVVLNSGEKGGDSFGVQIKGANDQGASGALSSDL ELPENPYSQVKGFPAPSQSSTSDEEPGAYWNGKLLRSHSQASLAGPGPV DPSNRSNSMLELAPKVASPGSTIDTAPLSSVDSLINKFDSQLGGQARGR TGRRTRMLPPEQRKRSKSLDSRLPRDTFEERERQSTNHWTSSTKYDNHV GTSKQPAQSQNLSPLSGFSRSRQTQDWVLQSFEEPRRSAQDPTMLQFKS TPDLLRDQQEAAPPGSVDHMKATIYGILREGSSESETSVRRKVSLVLEK MQPLVMVSSGSTKAVAGQGELTRKVEELQRKLDEEVKKRQKLEPSQVGL ERQLEEKTEECSRLQELLERRKGEAQQSNKELQNMKRLLDQGEDLRHGL ETQVMELQNKLKHVQGPEPAKEVLLKDLLETRELLEEVLEGKQRVEEQL RLRERELTALKGALKEEVASRDQEVEHVRQQYQRDTEQLRRSMQDATQD HAVLEAERQKMSALVRGLQRELEETSEETGHWQSMFQKNKEDLRATKQE LLQLRMEKEEMEEELGEKIEVLQRELEQARASAGDTRQVEVLKKELLRT QEELKELQAERQSQEVAGRHRDRELEKQLAVLRVEADRGRELEEQNLQL QKTLQQLRQDCEEASKAKMVAEAEATVLGQRRAAVETTLRETQEENDEF RRRILGLEQQLKETRGLVDGGEAVEARLRDKLQRLEAEKQQLEEALNAS QEEEGSLAAAKRALEARLEEAQRGLARLGQEQQTLNRALEEEGKQREVL RRGKAELEEQKRLLDRTVDRLNKELEKIGEDSKQALQQLQAQLEDYKEK ARREVADAQRQAKDWASEAEKTSGGLSRLQDEIQRLRQALQASQAERDT ARLDKELLAQRLQGLEQEAENKKRSQDDRARQLKGLEEKVSRLETELDE EKNTVELLTDRVNRGRDQVDQLRTELMQERSARQDLECDKISLERQNKD LKTRLASSEGFQKPSASLSQLESQNQLLQERLQAEEREKTVLQSTNRKL ERKVKELSIQIEDERQHVNDQKDQLSLRVKALKRQVDEAEEEIERLDGL RKKAQREVEEQHEVNEQLQARIKSLEKDSWRKASRSAAESALKNEGLSS DEEFDSVYDPSSIASLLTESNLQTSSC

[0505] Primers for amplifying the sequence CGN can be designed using primer design software such as Oligo Calc. Examples of primer pairs for amplifying CGN include those in

TABLE-US-00027 Forward SEQ ID NO: 67 GCTTTAGCCGTTCTCGTCA Reverse SEQ ID NO: 68 CTGGTCTCGAAGGAGGTCTG Forward SEQ ID NO: 69 CAGACCTCCTTCGAGACCAG Reverse SEQ ID NO: 70 TTCCTCCTCACAGAGGTTTCA Forward SEQ ID NO: 71 TACAGCGAAAGCTGGATGAA Reverse SEQ ID NO: 72 AGTCGGCTGCACTCTTCTGT Forward SEQ ID NO: 73 TGCAGAACAAGCTGAAACAT Reverse SEQ ID NO: 74 GCTGCTCCTCTACTCGCTGT Forward SEQ ID NO: 75 GGGCATTGGCAGAGTATGTT Reverse SEQ ID NO: 76 TTCCATCTCCTCCTTCTCCA Forward SEQ ID NO: 77 CAGCAACTGCGACAGGACT Reverse SEQ ID NO: 78 CATTTTCCTCCTGGGTCTCC Forward SEQ ID NO: 79: CTGAGCTGGAGGAGCAGAAG Reverse SEQ ID NO: 80 TGCAGGGCTTGCTTAGAGTC Forward SEQ ID NO: 81 TGGAGCAAGAGGCAGAGAAC Reverse SEQ ID NO: 82 ACTCTGTTTCCAGCCGTGAG

[0506] Probes for detecting CGN can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

TABLE-US-00028 SEQ ID NO: 83 CAGGACTGGGTCCTTCAGAG SEQ ID NO: 84 CAGGCAGTGTGGACCATATG SEQ ID NO: 85 GCTAGAGCCATCCCAAGTTG SEQ ID NO: 86 TGAGCCTGCTAAGGAGGTGT SEQ ID NO: 87 TAGAGCCACCAAGCAGGAAC SEQ ID NO: 88 TTCCAAGGCTAAGATGGTGG SEQ ID NO: 89 GACAGGACTGTGGACCGACT SEQ ID NO: 90 TGAAGGGTCTCGAGGAAAAA Probe from the array SEQ ID NO: 91 GGGAAGAGGTAAGGGGGATGATTCACCTCCATATTTCCTAAGCAGGTT GTATAGGGAGCC

[0507] Antibodies to CGN include, but are not limited to Rabbit Anti-Human Cingulin (CGN) Polyclonal, Unconjugated Cat# LS-C22229-100, from lifespan bioscience (C-terminal region); and Mouse Anti-Human Cingulin (CGN) Monoclonal, Unconjugated, Clone 6a40 Cat# LS-C22230-100, from Lifespan Bioscience (C-terminal region).

Example 10

DDR1

[0508] DDR1 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that DDR1 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue and it was surprisingly found that DDR1 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Examples 2-4. Example 5 shows that DDR1 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0509] The sequence of an mRNA corresponding to DDR1 is given in ENSEMBL accession no. ENST00000376570 and has a sequence as in SEQ ID NO:92

TABLE-US-00029 1 GTCTTCCCCTCGTGGGCCCTGAGCGGGACTGCAGCCAGCCCCCTGGGGCGCCAGCTTTG 61 AGGCCCCCGACAGCTGCTCTCGGGAGCCGCCTCCCGACACCCGAGCCCCGCCGGCGCCTC 121 CCGCTCCCGGCTCCCGGCTCCTGGCTCCCTCCGCCTCCCCCGCCCCTCGCCCCGCCGCC 181 AAGAGGCCCCGCTCCCGGGTCGGACGCCTGGGTCTGCCGGGAAGAGCGATGAGAGGTGTC 241 TGAAGGTGGCTATTCACTGAGCGATGGGGTTGGACTTGAAGGAATGCCAAGAGATGCTGC 301 CCCCACCCCCTTAGGCCCGAGGGATCAGGAGCTATGGGACCAGAGGCCCTGTCATCTTTA 361 CTGCTGCTGCTCTTGGTGGCAAGTGGAGATGCTGACATGAAGGGACATTTTGATCCTGCC 421 AAGTGCCGCTATGCCCTGGGCATGCAGGACCGGACCATCCCAGACAGTGACATCTCTGCT 481 TCCAGCTCCTGGTCAGATTCCACTGCCGCCCGCCACAGCAGGTTGGAGAGCAGTGACGGG 541 GATGGGGCCTGGTGCCCCGCAGGGTCGGTGTTTCCCAAGGAGGAGGAGTACTTGCAGGTG 601 GATCTACAACGACTGCACCTGGTGGCTCTGGTGGGCACCCAGGGACGGCATGCCGGGGGC 661 CTGGGCAAGGAGTTCTCCCGGAGCTACCGGCTGCGTTACTCCCGGGATGGTCGCCGCTGG 721 ATGGGCTGGAAGGACCGCTGGGGTCAGGAGGTGATCTCAGGCAATGAGGACCCTGAGGGA 781 GTGGTGCTGAAGGACCTTGGGCCCCCCATGGTTGCCCGACTGGTTCGCTTCTACCCCCGG 841 GCTGACCGGGTCATGAGCGTCTGTCTGCGGGTAGAGCTCTATGGCTGCCTCTGGAGGGAT 901 GGACTCCTGTCTTACACCGCCCCTGTGGGGCAGACAATGTATTTATCTGAGGCCGTGTAC 961 CTCAACGACTCCACCTATGACGGACATACCGTGGGCGGACTGCAGTATGGGGGTCTGGGC 1021 CAGCTGGCAGATGGTGTGGTGGGGCTGGATGACTTTAGGAAGAGTCAGGAGCTGCGGGTC 1081 TGGCCAGGCTATGACTATGTGGGATGGAGCAACCACAGCTTCTCCAGTGGCTATGTGGAG 1141 ATGGAGTTTGAGTTTGACCGGCTGAGGGCCTTCCAGGCTATGCAGGTCCACTGTAACAAC 1201 ATGCACACGCTGGGAGCCCGTCTGCCTGGCGGGGTGGAATGTCGCTTCCGGCGTGGCCCT 1261 GCCATGGCCTGGGAGGGGGAGCCCATGCGCCACAACCTAGGGGGCAACCTGGGGGACCCC 1321 AGAGCCCGGGCTGTCTCAGTGCCCCTTGGCGGCCGTGTGGCTCGCTTTCTGCAGTGCCGC 1381 TTCCTCTTTGCGGGGCCCTGGTTACTCTTCAGCGAAATCTCCTTCATCTCTGATGTGGTG 1441 AACAATTCCTCTCCGGCACTGGGAGGCACCTTCCCGCCAGCCCCCTGGTGGCCGCCTGGC 1501 CCACCTCCCACCAACTTCAGCAGCTTGGAGCTGGAGCCCAGAGGCCAGCAGCCCGTGGCC 1561 AAGGCCGAGGGGAGCCCGACCGCCATCCTCATCGGCTGCCTGGTGGCCATCATCCTGCTC 1621 CTGCTGCTCATCATTGCCCTCATGCTCTGGCGGCTGCACTGGCGCAGGCTCCTCAGCAAG 1681 GCTGAACGGAGGGTGTTGGAAGAGGAGCTGACGGTTCACCTCTCTGTCCCTGGGGACACT 1741 ATCCTCATCAACAACCGCCCAGGTCCTAGAGAGCCACCCCCGTACCAGGAGCCCCGGCCT 1801 CGTGGGAATCCGCCCCACTCCGCTCCCTGTGTCCCCAATGGCTCTGCCTACAGTGGGGAC 1861 TATATGGAGCCTGAGAAGCCAGGCGCCCCGCTTCTGCCCCCACCTCCCCAGAACAGCGTC 1921 CCCCATTATGCCGAGGCTGACATTGTTACCCTGCAGGGCGTCACCGGGGGCAACACCTAT 1588 CCCCATTATGCCGAGGCTGACATTGTTACCCTGCAGGGCGTCACCGGGGGCAACACCTAT 1981 GCTGTGCCTGCACTGCCCCCAGGGGCAGTCGGGGATGGGCCCCCCAGAGTGGATTTCCCT 1648 GCTGTGCCTGCACTGCCCCCAGGGGCAGTCGGGGATGGGCCCCCCAGAGTGGATTTCCCT 2041 CGATCTCGACTCCGCTTCAAGGAGAAGCTTGGCGAGGGCCAGTTTGGGGAGGTGCACCTG 1708 CGATCTCGACTCCGCTTCAAGGAGAAGCTTGGCGAGGGCCAGTTTGGGGAGGTGCACCTG 2101 TGTGAGGTCGACAGCCCTCAAGATCTGGTTAGTCTTGATTTCCCCCTTAATGTGCGTAAG 1768 TGTGAGGTCGACAGCCCTCAAGATCTGGTTAGTCTTGATTTCCCCCTTAATGTGCGTAAG 2161 GGACACCCTTTGCTGGTAGCTGTCAAGATCTTACGGCCAGATGCCACCAAGAATGCCAGG 1828 GGACACCCTTTGCTGGTAGCTGTCAAGATCTTACGGCCAGATGCCACCAAGAATGCCAGG 2221 AATGATTTCCTGAAAGAGGTGAAGATCATGTCGAGGCTCAAGGACCCAAACATCATTCGG 1888 AATGATTTCCTGAAAGAGGTGAAGATCATGTCGAGGCTCAAGGACCCAAACATCATTCGG 2281 CTGCTGGGCGTGTGTGTGCAGGACGACCCCCTCTGCATGATTACTGACTACATGGAGAAC 1948 CTGCTGGGCGTGTGTGTGCAGGACGACCCCCTCTGCATGATTACTGACTACATGGAGAAC 2341 GGCGACCTCAACCAGTTCCTCAGTGCCCACCAGCTGGAGGACAAGGCAGCCGAGGGGGCC 2008 GGCGACCTCAACCAGTTCCTCAGTGCCCACCAGCTGGAGGACAAGGCAGCCGAGGGGGCC 2401 CCTGGGGACGGGCAGGCTGCGCAGGGGCCCACCATCAGCTACCCAATGCTGCTGCATGTG 2068 CCTGGGGACGGGCAGGCTGCGCAGGGGCCCACCATCAGCTACCCAATGCTGCTGCATGTG 2461 GCAGCCCAGATCGCCTCCGGCATGCGCTATCTGGCCACACTCAACTTTGTACATCGGGAC 2128 GCAGCCCAGATCGCCTCCGGCATGCGCTATCTGGCCACACTCAACTTTGTACATCGGGAC 2521 CTGGCCACGCGGAACTGCCTAGTTGGGGAAAATTTCACCATCAAAATCGCAGACTTTGGC 2188 CTGGCCACGCGGAACTGCCTAGTTGGGGAAAATTTCACCATCAAAATCGCAGACTTTGGC 2581 ATGAGCCGGAACCTCTATGCTGGGGACTATTACCGTGTGCAGGGCCGGGCAGTGCTGCCC 2248 ATGAGCCGGAACCTCTATGCTGGGGACTATTACCGTGTGCAGGGCCGGGCAGTGCTGCCC 2641 ATCCGCTGGATGGCCTGGGAGTGCATCCTCATGGGGAAGTTCACGACTGCGAGTGACGTG 2308 ATCCGCTGGATGGCCTGGGAGTGCATCCTCATGGGGAAGTTCACGACTGCGAGTGACGTG 2701 TGGGCCTTTGGTGTGACCCTGTGGGAGGTGCTGATGCTCTGTAGGGCCCAGCCCTTTGGG 2368 TGGGCCTTTGGTGTGACCCTGTGGGAGGTGCTGATGCTCTGTAGGGCCCAGCCCTTTGGG 2761 CAGCTCACCGACGAGCAGGTCATCGAGAACGCGGGGGAGTTCTTCCGGGACCAGGGCCGG 2428 CAGCTCACCGACGAGCAGGTCATCGAGAACGCGGGGGAGTTCTTCCGGGACCAGGGCCGG 2821 CAGGTGTACCTGTCCCGGCCGCCTGCCTGCCCGCAGGGCCTATATGAGCTGATGCTTCGG 2488 CAGGTGTACCTGTCCCGGCCGCCTGCCTGCCCGCAGGGCCTATATGAGCTGATGCTTCGG 2881 TGCTGGAGCCGGGAGTCTGAGCAGCGACCACCCTTTTCCCAGCTGCATCGGTTCCTGGCA 2548 TGCTGGAGCCGGGAGTCTGAGCAGCGACCACCCTTTTCCCAGCTGCATCGGTTCCTGGCA 2941 GAGGATGCACTCAACACGGTGTGAATCACACATCCAGCTGCCCCTCCCTCAGGGAGCGAT 3001 CCAGGGGAAGCCAGTGACACTAAAACAAGAGGACACAATGGCACCTCTGCCCTTCCCCTC 3061 CCGACAGCCCATCACCTCTAATAGAGGCAGTGAGACTGCAGGTGGGCTGGGCCCACCCAG 3121 GGAGCTGATGCCCCTTCTCCCCTTCCTGGACACACTCTCATGTCCCCTTCCTGTTCTTCC 3181 TTCCTAGAAGCCCCTGTCGCCCACCCAGCTGGTCCTGTGGATGGGATCCTCTCCACCCTC 3241 CTCTAGCCATCCCTTGGGGAAGGGTGGGGAGAAATATAGGATAGACACTGGACATGGCCC 3301 ATTGGAGCACCTGGGCCCCACTGGACAACACTGATTCCTGGAGAGGTGGCTGCGCCCCCA 3361 GCTTCTCTCTCCCTGTCACACACTGGACCCCACTGGCTGAGAATCTGGGGGTGAGGAGGA 3421 CAAGAAGGAGAGGAAAATGTTTCCTTGTGCCTGCTCCTGTACTTGTCCTCAGCTTGGGCT 3481 TCTTCCTCCTCCATCACCTGAAACACTGGACCTGGGGGTAGCCCCGCCCCAGCCCTCAGT 3541 CACCCCCACTTCCCACTTGCAGTCTTGTAGCTAGAACTTCTCTAAGCCTATACGTTTCTG 3601 TGGAGTAAATATTGGGATTGGGGGGAAAGAGGGAGCAACGGCCCATAGCCTTGGGGTTGG 3661 ACATCTCTAGTGTAGCTGCCACATTGATTTTTCTATAATCACTTGGGGTTTGTACATTTT 3721 TGGGGGGAGAGACACAGATTTTTACACTAATATATGGACCTAGCTTGAGGCAATTTTAAT 3781 CCCCTGCACTAGGCAGGTAATAATAAAGGTTGAGTTTTCC

[0510] The corresponding amino acid sequence is given in ENSEMBL accession no. EP0000365754 and has a sequence as in SEQ ID NO:93

TABLE-US-00030 1 MGPEALSSLLLLLLVASGDADMKGHFDPAKCRYALGMQDRTIPDSDISASSSWSDSTAAR 61 HSRLESSDGDGAWCPAGSVFPKEEEYLQVDLQRLHLVALVGTQGRHAGGLGKEFSRSYRL 121 RYSRDGRRWMGWKDRWGQEVISGNEDPEGVVLKDLGPPMVARLVRFYPRADRVMSVCLRV 181 ELYGCLWRDGLLSYTAPVGQTMYLSEAVYLNDSTYDGHTVGGLQYGGLGQLADGVVGLDD 241 FRKSQELRVWPGYDYVGWSNHSFSSGYVEMEFEFDRLRAFQAMQVHCNNMHTLGARLPGG 301 VECRFRRGPAMAWEGEPMRHNLGGNLGDPRARAVSVPLGGRVARFLQCRFLFAGPWLLFS 361 EISFISDVVNNSSPALGGTFPPAPWWPPGPPPTNFSSLELEPRGQQPVAKAEGSPTAILI 421 GCLVAIILLLLLIIALMLWRLHWRRLLSKAERRVLEEELTVHLSVPGDTILINNRPGPRE 481 PPPYQEPRPRGNPPHSAPCVPNGSAYSGDYMEPEKPGAPLLPPPPQNSVPHYAEADIVTL 541 QGVTGGNTYAVPALPPGAVGDGPPRVDFPRSRLRFKEKLGEGQFGEVHLCEVDSPQDLVS 601 LDFPLNVRKGHPLLVAVKILRPDATKNARNDFLKEVKIMSRLKDPNIIRLLGVCVQDDPL 661 CMITDYMENGDLNQFLSAHQLEDKAAEGAPGDGQAAQGPTISYPMLLHVAAQIASGMRYL 721 ATLNFVHRDLATRNCLVGENFTIKIADFGMSRNLYAGDYYRVQGRAVLPIRWMAWECILM 781 GKFTTASDVWAFGVTLWEVLMLCRAQPFGQLTDEQVIENAGEFFRDQGRQVYLSRPPACP 841 QGLYELMLRCWSRESEQRPPFSQLHRFLAEDALNTV

[0511] Primers for amplifying the sequence DDR1 can be designed using primer design software such as Oligo Calc and/or Primer 3.

[0512] Examples of primer pairs for amplifying DDR1 include those in

TABLE-US-00031 Forward SEQ ID NO: 94 CATCTCTGCTTCCAGCTCCT Reverse SEQ ID NO: 95 TACTCCTCCTCCTTGGGAAA Forward SEQ ID NO: 96 AGCTACCGGCTGCGTTACT Reverse SEQ ID NO: 97 CTTCAGCACCACTCCCTCAG Forward SEQ ID NO: 98 CGTCTGTCTGCGGGTAGAG Reverse SEQ ID NO: 99 CCGTCATAGGTGGAGTCGTT Forward SEQ ID NO: 100 CAACGACTCCACCTATGACG Reverse SEQ ID NO: 101 TGCTCCATCCCACATAGTCA Forward SEQ ID NO: 102 TGACTATGTGGGATGGAGCA Reverse SEQ ID NO: 103 CCAGCGTGTGCATGTTGTTA Forward SEQ ID NO: 104 TGTCTCAGTGCCCCTTGG Reverse SEQ ID NO: 105 GTGCCGGAGAGGAATTGTT Forward SEQ ID NO: 106 ACCTCCCACCAACTTCAGC Reverse SEQ ID NO: 107 CAGCAGGAGCAGGATGATG Forward SEQ ID NO: 108 CATCATCCTGCTCCTGCTG Reverse SEQ ID NO: 109 CCAGGGACAGAGAGGTGAAC Forward SEQ ID NO: 110 ACCGCCCAGGTCCTAGAG Reverse SEQ ID NO: 111 CGGTAGGCTGGATTGGAGA Forward SEQ ID NO: 112 CACCCTTTGCTGGTAGCTGT Reverse SEQ ID NO: 113 CGAATGATGTTTGGGTCCTT

[0513] Probes for detecting DDR1 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

TABLE-US-00032 SEQ ID NO: 114 ACAGCAGGTTGGAGAGCAGT SEQ ID NO: 115 GTCAGGAGGTGATCTCAGGC SEQ ID NO: 116 CTCTATGGCTGCCTCTGGAG SEQ ID NO: 117 GTGGGGCTGGATGACTTTAG SEQ ID NO: 118 AGTTTGAGTTTGACCGGCTG SEQ ID NO: 119 CCCTGGTTACTCTTCAGCGA SEQ ID NO: 120 CTTGGAGCTGGAGCCCAG SEQ ID NO: 121 AGGGTGTTGGAAGAGGAGCT SEQ ID NO: 122 ACTCTGCTCCCTGTGTCCC SEQ ID NO: 123 GCCAGGAATGATTTCCTGAA

[0514] A probe used to detect the DDR1 nucleic acid that was used on the microarray has a sequence as in

TABLE-US-00033 SEQ ID NO: 124 ATTGGGATTGGGGGGAAAGAGGGAGCAACGGCCCATAGCCTTGGGGTTGG ACATCTCTAG

[0515] Other probes to DDR1 are known in the art and/or can be readily designed by the skilled artisan.

[0516] Antibodies against DDR1 include, but are not limited to, Rabbit polyclonal antibody to MCK10 from abcam cat# ab5508 epitope: aa31-47; and Mouse Anti-Human DDR1 Polyclonal Antibody, Unconjugated from abnova cat# H00000780-A01 against full length.

Example 11

EPS8L2

[0517] EPS8L2 (EPS8-like 2 also known as AI042819, AW545405, Eps812_predicted, Eps812 predicted, EPS8R2, FLJ16738, FLJ21935, FLJ22171, MGC126530, MGC3088)

was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that EPS8L2 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue and it was surprisingly found that EPS8L2 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Examples 2-4. Example 5 shows that EPS8L2 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0518] The EPS8L2 gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a substrate for the epidermal growth factor receptor. The eps8Ls define a novel family of proteins responsible for functional redundancy in the RTK-activated signaling pathway leading to actin remodeling. Members of this family link growth factor stimulation to actin organization. Members of the eps8 family share a modular organization consisting of a putative PTB domain, a central SH3 domain and a C-terminal effector region. The SH3 domains of eps8Ls display unique binding preferences for peptides containing a proline-X-X-aspartate-tyrosine (pXXDY) consensus and constitute a phylogenetically distinct subfamily within the SH3 domain family. (PMID: 14565974).

[0519] Although EPS8L2 function is unknown, gene expression analyses of breast and thyroid cancers identified Eps8, another member of the family, as a novel putative oncogene and also it was implicated in tumor cell migration in fibrosarcoma cells. (PMID: 16618726) (PMID: 17075124) (PMID: 15289329)

[0520] The sequence of an mRNA corresponding to EPS8L2 is given in ENSEMBL accession no. ENST00000318562 and SEQ ID NO:125

TABLE-US-00034 ACTCCGCAACCTGTCGCTCAGGTTCCTCCTCTCCCGGCCCCGCCCCGGC CCGGCCCCGCCGAGCGTCCCACCCGCCCGCGGGAGACCTGGCGCCCCGG CCGAGGCGCGAACAGACGGACGCACCGGCGAGCGCCGAGGGGACAGGCC GAGCGCGGGGCGCCGGAGGCAGGTGTGGGACAGGCACTGGCCTCAGACC GGGGCCACACTGAGGTCTGCCCTTCTCCCGCTGGCCGCCACCCAAGACA CCATGAGCCAGTCCGGGGCCGTGAGCTGCTGCCCGGGTGCCACCAATGG CAGCCTGGGCCGGTCCGACGGTGTGGCCAAGATGAGCCCCAAGGACCTG TTTGAGCAGAGGAAGAAGTATTCCAACTCCAACGTCATCATGCACGAGA CCTCGCAGTACCACGTCCAGCACCTGGCCACATTCATCATGGACAAGAG CGAAGCCATCACGTCTGTGGACGACGCCATCCGGAAGCTGGTGCAGCTG AGCTCCAAGGAGAAGATCTGGACCCAGGAGATGCTGCTGCAGGTGAACG ACCAGTCGCTGCGGCTGCTGGACATCGAGTCACAGGAGGAGCTGGAAGA CTTCCCGCTGCCCACGGTGCAGCGCAGCCAGACGGTCCTCAACCAGCTG CGCTACCCGTCTGTGCTGCTGCTCGTGTGCCAGGACTCGGAGCAGAGCA AGCCGGATGTCCACTTCTTCCACTGCGATGAGGTGGAGGCAGAGCTGGT GCACGAGGACATCGAGAGCGCGTTGGCCGACTGCCGGCTGGGCAAGAAG ATGCGGCCGCAGACCCTGAAGGGACACCAGGAGAAGATTCGGCAGCGGC AGTCCATCCTGCCTCCTCCCCAGGGCCCGGCGCCCATCCCCTTCCAGCA CCGCGGCGGGGATTCCCCGGAGGCCAAGAATCGCGTGGGCCCGCAGGTG CCACTCAGCGAGCCAGGTTTCCGCCGTCGGGAGTCGCAGGAGGAGCCGC GGGCCGTGCTGGCTCAGAAGATAGAGAAGGAGACGCAAATCCTCAACTG CGCCCTGGACGACATCGAGTGGTTTGTGGCCCGGCTGCAGAAGGCAGCC GAGGCTTTCAAGCAGCTGAACCAGCGGAAAAAGGGGAAGAAGAAGGGCA AGAAGGCGCCAGCAGAGGGCGTCCTCACACTGCGGGCACGGCCCCCCTC TGAGGGCGAGTTCATCGACTGCTTCCAGAAAATCAAGCTGGCGATTAAC TTGCTGGCAAAGCTGCAGAAGCACATCCAGAACCCCAGCGCCGCGGAGC TCGTGCACTTCCTCTTCGGGCCTCTGGACCTGATCGTCAACACCTGCAG TGGCCCAGACATCGCACGCTCCGTCTCCTGCCCACTGCTCTCCCGAGAT GCCGTGGACTTCCTGCGCGGCCACCTGGTCCCTAAGGAGATGTCGCTGT GGGAGTCACTGGGAGAGAGCTGGATGCGGCCCCGTTCCGAGTGGCCGCG GGAGCCACAGGTGCCCCTCTACGTGCCCAAGTTCCACAGCGGCTGGGAG CCTCCTGTGGATGTGCTGCAGGAGGCCCCCTGGGAGGTGGAGGGGCTGG CGTCTGCCCCCATCGAGGAGGTGAGTCCAGTGAGCCGACAGTCCATAAG AAACTCCCAGAAGCACAGCCCCACTTCAGAGCCCACCCCCCCGGGGGAT GCCCTACCACCAGTCAGCTCCCCACATACTCACAGGGGCTACCAGCCAA CACCAGCCATGGCCAAGTACGTCAAGATCCTGTATGACTTCACAGCCCG AAATGCCAACGAGCTATCGGTGCTCAAGGATGAGGTCCTAGAGGTGCTG GAGGACGGCCGGCAGTGGTGGAAGCTGCGCAGCCGCAGCGGCCAGGCGG GGTACGTGCCCTGCAACATCCTAGGCGAGGCGCGACCGGAGGACGCCGG CGCCCCGTTCGAGCAGGCCGGTCAGAAGTACTGGGGCCCCGCCAGCCCG ACCCACAAGCTACCCCCAAGCTTCCCGGGGAACAAAGACGAGCTCATGC AGCACATGGACGAGGTCAACGACGAGCTCATCCGGAAAATCAGCAACAT CAGGGCGCAGCCACAGAGGCACTTCCGCGTGGAGCGCAGCCAGCCCGTG AGCCAGCCGCTCACCTACGAGTCGGGTCCGGACGAGGTCCGCGCCTGGC TGGAAGCCAAGGCCTTCAGCCCGCGGATCGTGGAGAACCTGGGCATCCT GACCGGGCCGCAGCTCTTCTCCCTCAACAAGGAGGAGCTGAAGAAAGTG TGCGGCGAGGAGGGCGTCCGCGTGTACAGCCAGCTCACCATGCAGAAGG CCTTCCTGGAGAAGCAGCAAAGTGGGTCGGAGCTGGAAGAACTCATGAA CAAGTTTCATTCCATGAATCAGAGGAGGGGGGAGGACAGCTAGGCCCAG CTGCCTTGGGCTGGGGCCTGCGGAGGGGAAGCCCACCCACAATGCATGG AGTATTATTTTTATATGTGTATGTATTTTGTATCAAGGACACGGAGGGG GTGTGGTGCTGGCTAGAGGTCCCTGCCCCTGTCTGGAGGCACAACGCCC ATCCTTAGGCCAAACAGTACCCAAGGCCTCAGCCCACACCAAGACTAAT CTCAGCCAAACCTGCTGCTTGGTGGTGCCAGCCCCTTGTCCACCTTCTC TTGAGGCCACAGAACTCCCTGGGGCTGGGGCCTCTTTCTCTGGCCTCCC CTGTGCACCTGGGGGGTCCTGGCCCCTGTGATGCTCCCCCATCCCCACC CACTTCTACATCCATCCACACCCCAGGGTGAGCTGGAGCTCCAGGCTGG CCAGGCTGAACCTCGCACACACGCAGAGTTCTGCTCCCTGAGGGGGGCC CGGGAGGGGCTCCAGCAGGAGGCCGTGGGTGCCATTCGGGGGAAAGTGG GGGAACGACACACACTTCACCTGCAAGGGCCGACAACGCAGGGGACACC GTGCCGGCTTCAGACACTCCCAGCGCCCACTCTTACAGGCCCAGGACTG GAGCTTTCTCTGGCCAAGTTTCAGGCCAATGATCCCCGCATGGTGTTGG GGGTGCTGGTGTGTCTTGGTGCCTGGACTTGAGTCTCACCCTACAGATG AGAGGTGGCTGAGGCACCAGGGCTAAGCAATTAAACCAGTTAAGTCTCC CAGGAAAAAAAAAAAAAAAA

[0521] The start and stop codons are indicated in bold as well as the position corresponding to the microarray probe.

[0522] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000320828 and has a sequence as in SEQ ID NO:126

TABLE-US-00035 MSQSGAVSCCPGATNGSLGRSDGVAKMSPKDLFEQRKKYSNSNVIMHET SQYHVQHLATFIMDKSEAITSVDDAIRKLVQLSSKEKIWTQEMLLQVND QSLRLLDIESQEELEDFPLPTVQRSQTVLNQLRYPSVLLLVCQDSEQSK PDVHFFHCDEVEAELVHEDIESALADCRLGKKMRPQTLKGHQEKIRQRQ SILPPPQGPAPIPFQHRGGDSPEAKNRVGPQVPLSEPGFRRRESQEEPR AVLAQKIEKETQILNCALDDIEWFVARLQKAAEAFKQLNQRKKGKKKGK KAPAEGVLTLRARPPSEGEFIDCFQKIKLAINLLAKLQKHIQNPSAAEL VHFLFGPLDLIVNTCSGPDIARSVSCPLLSRDAVDFLRGHLVPKEMSLW ESLGESWMRPRSEWPREPQVPLYVPKFHSGWEPPVDVLQEAPWEVEGLA SAPIEEVSPVSRQSIRNSQKHSPTSEPTPPGDALPPVSSPHTHRGYQPT PAMAKYVKILYDFTARNANELSVLKDEVLEVLEDGRQWWKLRSRSGQAG YVPCNILGEARPEDAGAPFEQAGQKYWGPASPTHKLPPSFPGNKDELMQ HMDEVNDELIRKISNIRAQPQRHFRVERSQPVSQPLTYESGPDEVRAWL EAKAFSPRIVENLGILTGPQLFSLNKEELKKVCGEEGVRVYSQLTMQKA FLEKQQSGSELEELMNKFHSMNQRRGEDS

[0523] Primers for amplifying the sequence ENST00000318562 can be designed using primer design software such as Oligo Calc and/or Primer 3. Examples of primer pairs for amplifying EPS8L2 include:

TABLE-US-00036 Forward SEQ ID NO: 127 GAG ACC TGG CGC CCC GGC (Ex1) Reverse SEQ ID NO: 128 GTG GCC CCG GTC TGA GGC (Ex2) Forward SEQ ID NO: 129 GAG CCA GTC CGG GGC CGT G (Ex2) Reverse SEQ ID NO: 130 CTT GGG GCT CAT CTT GGC (Ex3) Forward SEQ ID NO: 131 CGA CGG TGT GGC CAA GAT GAG (Ex3 Reverse SEQ ID NO: 132 CGT GGT ACT GCG AGG TC (Ex4) Forward SEQ ID NO: 133 CTCCAACGTCATCATGCAC (Ex4) Reverse SEQ ID NO: 134 GATGGCGTCGTCCACAGAC (Ex5) Forward SEQ ID NO: 135 CAGTCGCTGCGGCTGCTGG (Ex5) Reverse SEQ ID NO: 136 GGACCGTCTGGCTGCGCTG (Ex6) Forward SEQ ID NO: 137 GATGTCCACTTCTTCCACTGC (Ex6) Reverse SEQ ID NO: 138 CCGAATCTTCTCCTGGTGTC (Ex8) Forward SEQ ID NO: 139 GAGGCCAAGAATCGCGTGGGC (Ex8) Reverse SEQ ID NO: 140 GTCCAGGGCGCAGTTGAGG (Ex10) Forward SEQ ID NO: 141 CGACTGCTTCCAGAAAATC (Ex11) Reverse SEQ ID NO: 142 CGAAGAGGAAGTGCACGAG (Ex12) Forward SEQ ID NO: 143 GATGTCGCTGTGGGAGTCAC (Ex13) Reverse SEQ ID NO: 144 GAGGGGCACCTGTGGCTC (Ex14) Forward SEQ ID NO: 145 GGTGGAGGGGCTGGCGTC (Ex14) Reverse SEQ ID NO: 146 GGCTCTGAAGTG GGGCTGTG (Ex15)

[0524] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0525] Probes for detecting EPS8L2 can be derived from any number of sources depending on the desired use (e.g., using the primers described above and the appropriate reagents).

[0526] Examples of probes include:

TABLE-US-00037 SEQ ID NO: 147 GCTTCCCGGGGAACAAAGACGAGCTCATGCAGCACATGGACGAGGTCAA CGACGAGCTCA SEQ ID NO: 148 GCAGAGCTGGTGCACGAGGACATCGAGAGCGCGTTGGCCGACTGCCGG SEQ ID NO: 149 GCCGTCGGGAGTCGCAGGAGGAGCCGCGGGCCGTGCTGGCTCAGAAGAT AG SEQ ID NO: 150 GCTCGTGTGCCAGGACTCGGAGCAGAGCAAGCCGGATGTCCAC SEQ ID NO: 151 GTACAGCCAGCTCACCATGCAGAAGGCCTTCCTGGAGAAGCAGCAAAG

[0527] Other probes to EPS8L2 are known in the art and/or can be readily designed by the skilled artisan.

[0528] Antibodies against EPS8L2 include, but are not limited to, Abnova Cat# H00064787-M01 which is a mouse monoclonal antibody raised against a partial recombinant EPS8L2 (615 a.a. .about.715 a.a) and Abnova Cat# H00064787-B01 which is a mouse polyclonal antibody raised against a full-length human EPS8L2 protein.

Example 12

FASTKD1

[0529] FASTKD1 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that FASTKD1 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue and it was surprisingly found that FASTKD1 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Examples 2-4. Example 5 shows that FASTKD1 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0530] The sequence of an mRNA corresponding to FASTKD1 is given in ENSEMBL accession no. ENST00000260971 and has a sequence as in SEQ ID NO:152

TABLE-US-00038 1 ATAAACCCTGAGATATGAGGGTTGGGCGAGACATCCGAGCCTGTTTCGTTCCGTGTTGGG 61 ACCAGGAATAACCCTGACTTCTGAGCTTTCATAACCCCAGGATCCTCCAGAAAATTTGCG 121 GCGCGCTGAGGGAAAACCTTGCTGAAGCTGTACATTGGAATGCGTTTACAGTCATTGTAA 181 TGGAAGCAAAATACATGAAGGAAAAACTGTTATTTGTATCCCTGCTTATTGCACCTGACG 241 ACTAGTTGCAGATGGTTTTGTTTACCTAAGAAAACTTGTGATATAAATGAAAAAAACACC 301 TGTTTTCCTAGAGTCATTGGTTACAAATATGCTTCGTCTAAGAGCTATTTGTCCATTCTC 361 CTGGAGAGTGTTTCAATTTCGACCCATCAGTTGTGAACCACTAATTATTCAGATGAATAA 421 GTGTACAGATGAGGAGCAAATGTTTGGTTTTATTGAAAGAAACAAAGCCATACTTTCAGA 481 AAAGCAAGTGGGATGTGCATTTGATATGCTTTGGAAGCTTCAAAAGCAGAAGACCAGCCT 541 GTTAAAAAATGCTGAGTATGTCAGAGACCATCCTCAATTTCTTACTCTTCATAATTTAGC 601 TACAAATAAATTCAAATTAATGAATGACGATACCCTGGTGAATGTGTTATACGTCACACA 661 ACAGTTTGCTGGTGAGGCCCATGACCCGCTAGTTGAAGCACTAGTTACAGAAGCATGGAG 721 AAGGCTAGAAAGGTTTGATATTAAACTGCTCTCAGAATTTTCCTCTTGCCTAGCAGATCA 781 GCATTTGTATTTTAGTCCATTAATGGGAAAAATAGCTGATATTGTTCATAGGACTTGGA 841 AACCACACAGGACTTAAGTTCCTTGTCTGTCTTGATGGTCAACATATCTTCTTTAATATC 901 ACGACATTTTCAACAACAACTGGTGAACAAAACAGAACTTCTTTTTGACACCATAGATTC 961 TTCTGAGGTCAACGTTGCAAAAGCATAGCAAAGTTTCTTCGAAATGTTAGATATCGTTA 1021 TCAACCACTATTAGAAAGATGTAATAACGTATTTTTAAGTAATGTGGACCACCTTGATTT 1081 GGATTCCATCAGTAAAATACTTAGTGTATACAAATTTCTACAATTTAATAGTTTTGAATT 1141 TATTATATGGCTAAAAAGAAGCTAACTGAAATGATTCCTCTGTGTAATCATCCTGCTAG 1201 CTTTGTAAAATTGTTTGTAGCATTGGGACCCATTGCAGGACCTGAAGAAAAGAAACAACT 1261 TAATCAACTATGTTATTGATGTCAGAGGACCTAACTGGCGAGCAAGCCCTGGCAGTGTT 1321 GGGAGCAATGGGAGATATGGAAAGCAGAAACTCATGTCTGATTAAAAGAGTTACTTCAGT 1381 TCTGCATAAACATTTGGATGGCTATAAACCATTAGAGTTGTTGAAGATAACTCAAGAATT 1441 AACTTTTCTGCATTTCCAAAGGAAGGAGTTTTTTGCGAAACTTAGAGAATTACTGCTTAG 1501 TTATTTGAAAAATAGTTTCATACCAACTGAGGTGTCTGTTCTGGTCCGTGCTATTTCCCT 1561 GCTCCCTTCTCCTCACTTGGACGAAGTGGGGATATCCCGAATTGAAGCCGTTTTACCACA 1621 GTGTGACCTAAATAACCTGAGTAGTTTTGCCACATCTGTTTTAAGATGGATTCAGCATGA 1681 TCACATGTATTTGGATAATATGACTGCGAAACAACTGAAACTACTTCAAAAATTAGATCA 1741 CTATGGTCGTCAGAGACTACAACACAGCAACAGTTTGGATCTGTTACGGAAGGAACTTAA 1801 ATCTCTCAAAGGAAACACGTTTCCTGAGTCACTTCTTGAAGAAATGATTGCTACTTTACA 1861 GCATTTCATGGATGATATTAATTACATAAATGTTGGGGAGATTGCATCTTTTATTCTAG 1921 TACTGATTACCTCAGTACTTTGCTACTAGATAGGATAGCCTCAGTGGCTGTTCAGCAGAT 1981 TGAAAGATCCATCCTTTTACAATCCCTGCTATTATTCGTCCATTCAGCGTATTGAACTA 2041 TGATCCACCTCAAAGGGATGAATTTTTGGGAACTTGCGTGCAACATCTTAATTCTTACTT 2101 AGGTATATTGGATCCTTTTATATTAGTGTTTCTTGGTTTCTCTTTGGCCACACTTGAATA 2161 TTTTCCAGAAGATCTGCTAAAGGCAATTTTTAACATCAAATTCTTAGCTAGATTGGATTC 2221 TCAACTTGAAAGTATTGGTGGCATGGATGGAACACAACAGCAGATTTTTAAAATGTTAGC 2281 AGAGGTACTAGGAGGAATCAATTGTGTAAAAGCCTCGGTTCTTACGCCTTATTACCACAA 2341 AGTAGATTTTGAGTGTATCTTGGATAAAAGAAAAAAACCTCTTCCGTATGGAAGCCATAA 2401 TATAGCATTGGGACAACTACCAGAAATGCCCTGGGAATCAAATATCGAAATAGTTGGATC 2461 AAGGCTGCCACCAGGGGCTGAAAGGATTGCTTTGGAATTTTTGGATTCAAAAGCACTTTG 2521 TAGAAATATCCCTCACATGAAAGGAAAATCTGCTATGAAAAAACGACATTTGGAAATTCT 2581 GGGTATCGTGTAATTCAGATTTCCCAGTTTGAATGGAACTCTATGGCACTGTCAACAAA 2641 GGATGCTCGGATGGACTACCTGAGAGAATGTATATTTGGAGAAGTCAAGTCATGTTTGTA 2701 GTTTTTATTTAAAATGAATGTTATCGTGTGTTACATTTGGACCTATTTTAATAAAGTGGC 2761 CTGTCTC

[0531] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000260971 and has a sequence as in SEQ ID NO:153

TABLE-US-00039 1 MKKTPVFLESLVTNMLRLRAICPFSWRVFQFRPISCEPLIIQMNKCTDEEQMFGFIERNK 61 AILSEKQVGCAFDMLWKLQKQKTSLLKNAEYVRDHPQFLTLHNLATNKFKLMNDDTLVNV 121 LYVTQQFAGEAHDPLVEALVTEAWRRLERFDIKLLSEFSSCLADQHLYFSPLMGKIADIV 181 HRNLETTQDLSSLSVLMVNISSLISRHFQQQLVNKTELLFDTIDSSEVNVAKSIAKFLRN 241 VRYRYQPLLERCNNVFLSNVDHLDLDSISKILSVYKFLQFNSFEFIIMAKKKLTEMIPLC 301 NHPASFVKLFVALGPIAGPEEKKQLKSTMLLMSEDLTGEQALAVLGAMGDMESRNSCLIK 361 RVTSVLHKHLDGYKPLELLKITQELTFLHFQRKEFFAKLRELLLSYLKNSFIPTEVSVLV 421 RAISLLPSPHLDEVGISRIEAVLPQCDLNNLSSFATSVLRWIQHDHMYLDNMTAKQLKLL 481 QKLDHYGRQRLQHSNSLDLLRKELKSLKGNTFPESLLEEMIATLQHFMDDINYINVGEIA 541 SFISSTDYLSTLLLDRIASVAVQQIEKIHPFTIPAIIRPFSVLNYDPPQRDEFLGTCVQH 601 LNSYLGILDPFILVFLGFSLATLEYFPEDLLKAIFNIKFLARLDSQLESIGGMDGTQQQI 661 FKMLAEVLGGINCVKASVLTPYYHKVDFECILDKRKKPLPYGSHNIALGQLPEMPWESNI 721 EIVGSRLPPGAERIALEFLDSKALCRNIPHMKGKSAMKKRHLEILGYRVIQISQFEWNSM 781 ALSTKDARMDYLRECIFGEVKSCL

[0532] Primers for amplifying a FASTKD1 nucleic acid sequence can be designed using primer design software such as Oligo Calc and/or Primer 3.

[0533] Examples of primer pairs for amplifying a FASTKD1 nucleic acid include those in

TABLE-US-00040 Forward: SEQ ID NO: 154 TGAATGACGATACCCTGGTG Reverse: SEQ ID NO: 155 AGCCTTCTCCATGCTTCTGT Forward: SEQ ID NO: 156 CCATGACCCGCTAGTTGAAG Reverse: SEQ ID NO: 157 TGATCTGCTAGGCAAGAGGAA Forward: SEQ ID NO: 158 TTCCTCTTGCCTAGCAGATCA Reverse: SEQ ID NO: 159 TGTTGACCATCAAGACAGACA Forward: SEQ ID NO: 160 TCCTCTGTGTAATCATCCTGCT Reverse: SEQ ID NO: 161 CTCGCCAGTTAGGTCCTCTG Forward: SEQ ID NO: 162 GGAGCAATGGGAGATATGGA Reverse: SEQ ID NO: 163 TTCCTTTGGAAATGCAGAAAA Forward: SEQ ID NO: 164 TGCATTTCCAAAGGAAGGAG Reverse: SEQ ID NO: 165 CAAGTGAGGAGAAGGGAGCA Forward: SEQ ID NO: 166 AAATGTTGGGGAGATTGCAT Reverse: SEQ ID NO: 167 TCAATACGCTGAATGGACGA Forward: SEQ ID NO: 168 GATCCACCTCAAAGGGATGA Reverse: SEQ ID NO: 169 GGCCAAAGAGAAACCAAGAA Forward: SEQ ID NO: 170 GTGTTTCTTGGTTTCTCTTTGG Reverse: SEQ ID NO: 171 CTGTTGTGTTCCATCCATGC Forward: SEQ ID NO: 172 GCATTGGGACAACTACCAGAA Reverse: SEQ ID NO: 173 GTATGGGAGCGCAAAAGAAG Forward: SEQ ID NO: 174 TGTGTTGCTTCATATTTGTACCC Reverse: SEQ ID NO: 175 CATAGCAGATTTTCCTTTCATGTG Forward: SEQ ID NO: 176 TGACCGCTTCTGTCAACAAT Reverse: SEQ ID NO: 177 TGAATCCAAAAATTCCAAAGC

[0534] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0535] Probes for detecting FASTKD1 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

TABLE-US-00041 SEQ ID NO: 178 GACCCGCTAGTTGAAGCACT SEQ ID NO: 179 ACAGAAGCATGGAGAAGGCT SEQ ID NO: 180 GAACTTGGAAACCACACAGGA SEQ ID NO: 181 TTGTAGCATTGGGACCCATT SEQ ID NO: 182 TGCATAAACATTTGGATGGC SEQ ID NO: 183 TTCTGGTCCGTGCTATTTCC SEQ ID NO: 184 GTGGCTGTTCAGCAGATTGA SEQ ID NO: 185 GAACTTGCGTGCAACATCTT SEQ ID NO: 186 CCAGAAGATCTGCTAAAGGCA SEQ ID NO: 187 TGCCCTGGGAATCAAATATC SEQ ID NO: 188 GGATTGCTTTGGAATTTTTGG SEQ ID NO: 189 ATGGATGGAACACAACAGCA

[0536] A probe for detecting a FASTKD1 nucleic acid that was used on the microarray has a sequence as in

TABLE-US-00042 SEO ID NO: 190 TGAATGGAACTCTATGGCACTGTCAACAAAGGATGCTCGGATGGACTACC TGAGAGA

[0537] Other probes to FASTKD1 are known in the art and/or can be readily designed by the skilled artisan.

[0538] Antibodies against FASTKD1 include, but are not limited to, Mouse Anti-Human FLJ21901 Polyclonal Antibody Cat# H00079675-A01 against de N-terminal (from aa 2-100).

Example 13

IKBKE

[0539] IKBKE (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon) also known as IKK-I; IKKE; IKKI; KIAA0151; MGC125294; MGC125295; MGC125297, was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that IKBKE was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue and it was surprisingly found that IKBKE was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that IKBKE can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0540] IKBKE is a member of the large IkB kinase complex capable of phosphorylating IkB. IKK phosphorylates only one of two serine residues in I.kappa.B.alpha. necessary for ubiquitination and degradation of I.kappa.B.alpha.. The degradation of IkB.alpha. exposes however, the nuclear localization signals on NF-kB, leading to its translocation to the nucleus, where it binds to specific promoters and activates transcription. (PMID: 10882136).

[0541] The sequence of an mRNA corresponding to IKBKE is given in ENSEMBL accession no. ENST00000367120 and has a sequence as in SEQ ID NO:191

TABLE-US-00043 GAGAGAGCTGAGAGCCAGGACTCAGTGCTGAGCTTGGTGTCCCACCGCCA CAAGGAGGCAGGGAAGAAACCCACTAGTCCCAGCTCCTGGGGTGGCACAG ACATTGCAACTGGCCCTGCCTGTGGGTCCTAGGGGCCCTTGGCTACCAGG AGGCTAAGAACACTGCTCATGAATGACAGTGAGCCCTGAAAGCTCTGGGG GTGTCACCCAGTCCCACAAGCCTGCATCCCCTGCAGTGGAGATGGGCTCA GCTCCTGGACGTGCCACAGACAGAAAGCATAACATACACTCGCCAGGAAG AGCCTTTGCCTGACTCAGGGCAGCTCAGAGTGTGGGGCAGAAGGTGACCA GCCAGCTCAGGGCAGGAGATGCAGAGCACAGCCAATTACCTGTGGCACAC AGATGACCTGCTGGGGCAGGGGGCCACTGCCAGTGTGTACAAGGCCCGCA ACAAGAAATCCGGAGAGCTGGTTGCTGTGAAGGTCTTCAACACTACCAGC TACCTGCGGCCCCGCGAGGTGCAGGTGAGGGAGTTTGAGGTCCTGCGGAA GCTGAACCACCAGAACATCGTCAAGCTCTTTGCGGTGGAGGAGACGGGCG GAAGCCGGCAGAAGGTACTGGTGATGGAGTACTGCTCCAGTGGGAGCCTG CTGAGTGTGCTGGAGAGCCCTGAGAATGCCTTTGGGCTGCCTGAGGATGA GTTCCTGGTGGTGCTGCGCTGTGTGGTGGCCGGCATGAACCACCTGCGGG AGAACGGCATTGTGCATCGCGACATCAAGCCGGGGAACATCATGCGCCTC GTAGGGGAGGAGGGGCAGAGCATCTACAAGCTGACAGACTTCGGCGCTGC CCGGGAGCTGGATGATGATGAGAAGTTCGTCTCGGTCTATGGGACTGAGG AGTACCTGCATCCCGACATGTATGAGCGGGCGGTGCTTCGAAAGCCCCAG CAAAAAGCGTTCGGGGTGACTGTGGATCTCTGGAGCATTGGAGTGACCTT GTACCATGCAGCCACTGGCAGCCTGCCCTTCATCCCCTTTGGTGGGCCAC GGCGGAACAAGGAGATCATGTACCGGATCACCACGGAGAAGCCGGCTGGG GCCATTGCAGGTGCCCAGAGGCGGGAGAACGGGCCCCTGGAGTGGAGCTA CACCCTCCCCATCACCTGCCAGCTGTCACTGGGGCTGCAGAGCCAGCTGG TGCCCATCCTGGCCAACATCCTGGAGGTGGAGCAGGCCAAGTGCTGGGGC TTCGACCAGTTCTTTGCGGAGACCAGTGACATCCTGCAGCGAGTTGTCGT CCATGTCTTCTCCCTGTCCCAGGCAGTCCTGCACCACATCTATATCCATG CCCACAACACGATAGCCATTTTCCAGGAGGCCGTGCACAAGCAGACCAGT GTGGCCCCCCGACACCAGGAGTACCTCTTTGAGGGTCACCTCTGTGTCCT CGAGCCCAGCGTCTCAGCACAGCACATCGCCCACACGACGGCAAGCAGCC CCCTGACCCTCTTCAGCACAGCCATCCCTAAGGGGCTGGCCTTCAGGGAC CCTGCTCTGGACGTCCCCAAGTTCGTCCCCAAAGTGGACCTGCAGGCGGA TTACAACACTGCCAAGGGCGTGTTGGGCGCCGGCTACCAGGCCCTGCGGC TGGCACGGGCCCTGCTGGATGGGCAGGAGCTAATGTTTCGGGGGCTGCAC TGGGTCATGGAGGTGCTCCAGGCCACATGCAGACGGACTCTGGAAGTGGC AAGGACATCCCTCCTCTACCTCAGCAGCAGCCTGGGAACTGAGAGGTTCA GCAGCGTGGCTGGAACGCCTGAGATCCAGGAACTGAAGGCGGCTGCAGAA CTGAGGTCCAGGCTGCGGACTCTAGCGGAGGTCCTCTCCAGATGCTCCCA AAATATCACGGAGACCCAGGAGAGCCTGAGCAGCCTGAACCGGGAGCTGG TGAAGAGCCGGGATCAGGTACATGAGGACAGAAGCATCCAGCAGATTCAG TGCTGTTTGGACAAGATGAACTTCATCTACAAACAGTTCAAGAAGTCTAG GATGAGGCCAGGGCTTGGCTACAACGAGGAGCAGATTCACAAGCTGGATA AGGTGAATTTCAGTCATTTAGCCAAAAGACTCCTGCAGGTGTTCCAGGAG GAGTGCGTGCAGAAGTATCAAGCGTCCTTAGTCACACACGGCAAGAGGAT GAGGGTGGTGCACGAGACCAGGAACCACCTGCGCCTGGTTGGCTGTTCTG TGGCTGCCTGTAACACAGAAGCCCAGGGGGTCCAGGAGAGTCTCAGCAAG CTCCTGGAAGAGCTATCTCACCAGCTCCTTCAGGACCGAGCAAAGGGGGC TCAGGCCTCGCCGCCTCCCATAGCTCCTTACCCCAGCCCTACACGAAAGG ACCTGCTTCTCCACATGCAAGAGCTCTGCGAGGGGATGAAGCTGCTGGCA TCTGACCTCCTGGACAACAACCGCATCATCGAACGGCTAAATAGAGTCCC AGCACCTCCTGATGTCTGAGCTCCATGGGGCACATGAGGCATCCTGAAGC ATTAGAATGATTCCAACACTGCTCTTCTGCACCATGAGACCAACCCAGGG CAAGATCCCATCCCATCACATCAGCCTACCTCCCTCCTGGCTGCTGGCCA GGATGTCGCCAGCATTACCTTCCACTGCCTTTCTCCCTGGGAAGCAGCAC AGCTGAGACTGGGCACCAGGCCACCTCTGTTGGGACCCACAGGAAAGAGT GTGGCAGCAACTGCCTGGCTGACCTTTCTATCTTCTCTAGGCTCAGGTAC TGCTCCTCCATGCCCATGGCTGGGCCGTGGGGAGAAGAAGCTCTCATACG CCTTCCCACTCCCTCTGGTTTATAGGACTTCACTCCCTAGCCAACAGGAG AGGAGGCCTCCTGGGGTTTCCCCAGGGCAGTAGGTCAAACGACCTCATCA CAGTCTTCCTTCCTCTTCAAGCGTTTCATGTTGAACACAGCTCTCTCCGC TCCCTTGTGATTTCTGAGGGTCACCACTGCCAGCCTCAGGCAACATAGAG AGCCTCCTGTTCTTTCTATGCTTGGTCTGACTGAGCCTAAAGTTGAGAAA ATGGGTGGCCAAGGCCAGTGCCAGTGTCTTGGGGCCCCTTTGGCTCTCCC TCACTCTCTGAGGCTCCAGCTGGTCCTGGGACATGCAGCCAGGACTGTGA GTCTGGGCAGGTCCAAGGCCTGCACCTTCAAGAAGTGGAATAAATGTGGC CTTTGCTTCTGTT

[0542] The start and stop codons are indicated in bold.

[0543] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000356087 and has a sequence as in SEQ ID NO:192

TABLE-US-00044 MQSTANYLWHTDDLLGQGATASVYKARNKKSGELVAVKVFNTTS YLRPREVQVREFEVLRKLNHQNIVKLFAVEETGGSRQKVLVMEYCSSGSL LSVLESPENAFGLPEDEFLVVLRCVVAGMNHLRENGIVHRDIKPGNIMRL VGEEGQSIYKLTDFGAARELDDDEKFVSVYGTEEYLHPDMYERAVLRKPQ QKAFGVTVDLWSIGVTLYHAATGSLPFIPFGGPRRNKEIMYRITTEKPAG AIAGAQRRENGPLEWSYTLPITCQLSLGLQSQLVPILANILEVEQAKCWG FDQFFAETSDILQRVVVHVFSLSQAVLHHIYIHAHNTIAIFQEAVHKQTS VAPRHQEYLFEGHLCVLEPSVSAQHIAHTTASSPLTLFSTAIPKGLAFRD PALDVPKFVPKVDLQADYNTAKGVLGAGYQALRLARALLDGQELMFRGLH WVMEVLQATCRRTLEVARTSLLYLSSSLGTERFSSVAGTPEIQELKAAAE LRSRLRTLAEVLSRCSQNITETQESLSSLNRELVKSRDQVHEDRSIQQIQ CCLDKMNFIYKQFKKSRMRPGLGYNEEQIHKLDKVNFSHLAKRLLQVFQE ECVQKYQASLVTHGKRMRVVHETRNHLRLVGCSVAACNTEAQGVQESLSK LLEELSHQLLQDRAKGAQASPPPIAPYPSPTRKDLLLHMQELCEGMKLLA SDLLDNNRIIERLNRVPAPPDV

[0544] Primers for amplifying the sequence ENST00000367120 can be designed using primer design software such as Oligo Calc and/or Primer 3.

[0545] Examples of primer pairs for amplifying IKBKE include:

TABLE-US-00045 Forward SEQ ID NO: 193 GTGCCACAGACAGAAAGCATAAC (EX2) Reverse SEQ ID NO: 194 GGCTGTGCTCTGCATCTC (ex3) Foward SEQ ID NO: 195 GGGGCCACTGCCAGTGTG (ex3) Reverse SEQ ID NO: 196 GCAGGTAGCTGGTAGTGTTGAAG (ex4) Forward SEQ ID NO: 197 GAGGTCCTGCGGAAGCTGAAC (ex4) Reverse SEQ ID NO: 198 CACTCAGCAGGCTCCCACTG (ex5) Forward SEQ ID NO: 199 CCTGAGGATGAGTTCCTGGTG (ex5) Reverse SEQ ID NO: 200 GTCGCGATGCACAATGCCGTTC (ex6) Forward SEQ ID NO: 201 GGATGATGATGAGAAGTTCGTCTC Reverse SEQ ID NO: 202 GAACGCTTTTTGCTGGGGC (ex7) Forward SEQ ID NO: 203 CATCCCCTTTGGTGGGCCAC (ex7) Reverse SEQ ID NO: 204 CCGTTCTCCCGCCTCTGG (ex8) Forward SEQ ID NO: 205 CCTGGAGTGGAGCTACACC (ex8) Reverse SEQ ID NO: 206 CACTTGGCCTGCTCCACCTC (ex9) Forward SEQ ID NO: 207 GTCCCAGGCAGTCCTGCAC (ex9) Reverse SEQ ID NO: 208 GACGCTGGGCTCGAGGACAC (ex10) Forward SEQ ID NO: 209 GACCCTCTTCAGCACAGCCAT C Reverse SEQ ID NO: 210 GCCGCAGGGCCTGGTAGC (ex12) Forward SEQ ID NO: 211 GATCCAGGAACTGAAGGCGGC (ex14) Reverse SEQ ID NO: 212 CCTGATCCCGGCTCTTCAC (ex15)

[0546] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0547] Probes for detecting IKBKE can be derived from any number of sources depending on the desired use (e.g., using the primers described above and the appropriate reagents).

[0548] Other examples of probes include:

TABLE-US-00046 SEQ ID NO: 213 CTCCTGTTCTTTCTATGCTTGGTCTGACTGAGCCTAAAGTTGAGAAAATG GGTGGCCAAG SEQ ID NO: 214 CATCACCTGCCAGCTGTCACTGGGGCTGCAGAGCC SEQ ID NO: 215 CTATATCCATGCCCACAACACGATAGCCATTTTCC SEQ ID NO: 216 GGACGTCCCCAAGTTCGTCCCCAAAGTGGACCTGCAGGCG SEQ ID NO: 217 GGTCCAGGAGAGTCTCAGCAAGCTCCTGGAAGAGCTATCTCAC

[0549] Other probes to IKBKE are known in the art and/or can be readily designed by the skilled artisan.

[0550] Antibodies against IKBKE include, but are not limited to, Abcam Cat# ab37596 which is a rabbit polyclonal antibody with an antigen that was a KLH conjugated synthetic peptide selected within a.a. 700-800 of human IKKE; and Abcam Cat# ab12142 which is a mouse monoclonal antibody against a synthetic peptide corresponding to a.a. residues 175-188, 525-540, or 567-580 of human IKK iota/IKK epsilon.

Example 14

PHKG2

[0551] PHKG2 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that PHKG2 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue and it was surprisingly found that PHKG2 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Examples 2-4. Example 5 shows that PHKG2 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0552] The sequence of an mRNA corresponding to PHKG2 is given in ENSEMBL accession no. ENST00000328273 and has a sequence as in SEQ ID NO:218

TABLE-US-00047 1 AAGGTGAGCGACTGCAGGCAAACCCGGCGACAGCGCAGCTCGCGTCGACCCTGGCTCCTC 61 TGCCTGCCCCCTCAGGCCCCCGCCTCCTTCAGGATGACGCTGGACGTGGGGCCGGAGGAT 121 GAGCTGCCCGACTGGGCCGCCGCCAAAGATTTTACCAGAAGTACGACCCTAAGGACGTC 181 ATCGGCAGAGGAGTGAGCTCTGTGGTCCGCCGTTGTGTTCATCGAGCTACTGGCCACGAG 241 TTTGCGGTGAAGATTATAGGAAGTGACAGCTGAGCGGCTGAGTCCTGAGCAGCTGGAGGAG 301 GTGCGGGAAGCCACACGGCGAGAGACACACATCCTTCGCCAGGTCGCCGGCCACCCCCAC 361 ATCATCACCCTCATCGATTCCTACGAGTCTTCTAGCTTCATGTTCCTGGTGTTTGACCTG 421 ATGCGGAAGGGAGAGCTGTTTGACTATCTCACAGAGAAGGTGGCCCTCTCTGAAAAGGAA 481 ACCAGGTCCATCATGCGGTCTCTGCTGGAAGCAGTGAGCTTTCTCCATGCCAACAACATT 541 GTGCATCGAGATCTGAAGCCCGAGAATATTCTCCTAGATGACAATATGCAGATCCGACTT 601 TCAGATTTCGGGTTCTCCTGCCACTTGGAACCTGGCGAGAAGCTTCGAGAGTTGTGTGGG 661 ACCCCAGGGTATCTAGCGCCAGAGATCCTTAAATGCTCCATGGATGAAACCCACCCAGGC 721 TATGGCAAGGAGGTCGACCTCTGGGCCTGTGGGGTGATCTTGTTCACACTCCTGGCTGGC 781 TCGCCACCCTTCTGGCACCGGCGGCAGATCCTGATGTTACGCATGATCATGGAGGGCCAG 841 TACCAGTTCAGTTCCCCCGAGTGGGATGACCGTTCCAGCACTGTCAAAGACCTGATCTCC 901 AGGCTGCTGCAGGTGGATCCTGAGGCACGCCTGACAGCTGAGCAGGCCCTACAGCACCCC 961 TTCTTTGAGCGTTGTGAAGGCAGCCAACCCTGGAACCTCACCCCCCGCCAGCGGTTCCGG 1021 GTGGCAGTGTGGACAGTGCTGGCTGCTGGACGAGTGGCCCTAAGCACCCATCGTGTACGG 1081 CCACTGACCAAGAATGCACTGTTGAGGGACCCTTATGCGCTGCGGTCAGTGCGGCACCTC 1141 ATCGACAACTGTGCCTTCCGGCTCTACGGGCACTGGGTAAAGAAAGGGGAGCAGCAGAAC 1201 CGGGCGGCTCTCTTTCAGCACCGGCCCCCTGGGCCTTTTCCCATCATGGGCCCTGAAGAG 1261 GAGGGAGACTCTGCTGCTATAACTGAGGATGAGGCCGTGCTTGTGCTGGGCTAGGACCTC 1321 AACCCCAGGGATTCCCAGGAAGCAGAACTCTCCAGAAGAAGGGTTTTGATCATTCCAGCT 1381 CCTCTGGGCTCTGGCCTCTGGCCTCAGGCCCACTAATGATCCTGCTACCCTCTTGAAGAC 1441 CAGCCCGGTACCTCTCTCCCCACTGGCCAGGACTCTGAGATCAGAGCTGGGGTGGAAGGG 1501 AGCCATTCTGAACGCCACGCCTGGCCCGGTCAGTGCTGCATGCACTGCATATGAAATAAA 1561 ATCTGCTACACGCCAGGG

[0553] The start and stop codons are indicated in bold.

[0554] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000329968 and has a sequence as in SEQ ID NO:219

TABLE-US-00048 1- MTLDVGPEDELPDWAAAKEFYQKYDPKDVIGRGVSSVVRRCVHRATGHEFAVKIMEVTAE 61 RLSPEQLEEVREATRRETHILRQVAGHPHIITLIDSYESSSFMFLVFDLMRKGELFDYLT 121 EKVALSEKETRSIMRSLLEAVSFLHANNIVHRDLKPENILLDDNMQIRLSDFGFSCHLEP 181 GEKLRELCGTPGYLAPEILKCSMDETHPGYGKEVDLWACGVILFTLLAGSPPFWHRRQIL 241 MLRMIMEGQYQFSSPEWDDRSSTVKDLISRLLQVDPEARLTAEQALQHPFFERCEGSQPW 301 NLTPRQRFRVAVWTVLAAGRVALSTHRVRPLTKNALLRDPYALRSVRHLIDNCAFRLYGH 361 WVKKGEQQNRAALFQHRPPGPFPIMGPEEEGDSAAITEDEAVLVLG

[0555] Primers for amplifying the sequence PHKG2 can be designed using primer design software such as Oligo Calc.

[0556] Examples of primer pairs for amplifying PHKG2 include those in

TABLE-US-00049 forward SEQ ID NO: 220 CCGCCAAAGAGTTTTACCAG reverse SEQ ID NO: 221 TCCATAATCTTCACCGCAAA forward SEQ ID NO: 222 GGCGAGAGACACACATCCTT reverse SEQ ID NO: 223 CAAACACCAGGAACATGAAGC forward SEQ ID NO: 224 GCTTCATGTTCCTGGTGTTTG reverse SEQ ID NO: 225 TTTTCAGAGAGGGCCACCTT forward SEQ ID NO: 226 GGAAGGGAGAGCTGTTTGACT reverse SEQ ID NO: 227 TGTTGTTGGCATGGAGAAAG forward SEQ ID NO: 228 TCAGATTTCGGGTTCTCCTG reverse SEQ ID NO: 229 ATAGCCTGGGTGGGTTTCAT forward SEQ ID NO: 230 ATGAAACCCACCCAGGCTAT reverse SEQ ID NO: 231 TGCGTAACATCAGGATCTGC forward SEQ ID NO: 232 CGTTCCAGCACTGTCAAAGA reverse: SEQ ID NO: 233 CCTTCACAACGCTCAAAGAA forward SEQ ID NO: 234 ACCCCTTCTTTGAGCGTTGT reverse SEQ ID NO: 235 CGTACACGATGGGTGCTTAG

[0557] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0558] Probes for detecting PHKG2 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

TABLE-US-00050 SEQ ID NO: 236 CCGTTGTGTTCATCGAGCTA SEQ ID NO: 237 CATCACCCTCATCGATTCCT SEQ ID NO: 238 GGAAGGGAGAGCTGTTTGACT SEQ ID NO: 239 AGGAAACCAGGTCCATCATG SEQ ID NO: 240 CAGGGTATCTAGCGCCAGAG SEQ ID NO: 241 CCTGTGGGGTGATCTTGTTC SEQ ID NO: 242 ACAGCTGAGCAGGCCCTAC SEQ ID NO: 243 GTTGTGGCAGTGTGGACAGT

[0559] A probe for detecting a PHKG2 nucleic acid that was used on the microarray has a sequence as in

TABLE-US-00051 SEQ ID NO: 244 CTCAACCCCAGGGATTCCCAGGAAGCAGAACTCTCCAGAAGAAGGGTTTT GATCATTCCA

[0560] Other probes to PHKG2 are known in the art and/or can be readily designed by the skilled artisan.

[0561] Antibodies against PHKG2 include, but are not limited to, Mouse monoclonal antibody Anti-PHKG2 against full length protein Cat# WH0005261M1 from SIGMA; PHKG2 antibody--N-terminal Cat# ab71129 from abcam; and PHKG2 antibody Cat# ab28642 against a region between amino acids 8-57 of human PHKG2 from abcam.

Example 15

P4HB

[0562] P4HB was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that P4HB was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue and it was surprisingly found that P4HB was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Examples 2-4. Example 5 shows that P4HB can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0563] The sequence of an mRNA corresponding to P4HB is given in ENSEMBL accession no. ENST00000331483 and has a sequence as in SEQ ID NO:245

TABLE-US-00052 1 GAGCCTCGAAGTCCGCCGGCCAATCGAAGGCGGGCCCCAGCGGCGCGTGCGCGCCGCGGC 61 CAGCGCGCGCGGGCGGGGGGGCAGGCGCGCCCCGGACCCAGGATTTATAAAGGCGAGGCC 121 GGGACCGGCGCGCGCTCTCGTCGCCCCCGCTGTCCCGGCGGCGCCAACCGAAGCGCCCCG 181 CCTGATCCGTGTCCGACATGCTGCGCCGCGCTCTGCTGTGCCTGGCCGTGGCCGCCCTGG 241 TGCGCGCCGACGCCCCCGAGGAGGAGGACCACGTCCTGGTGCTGCGGAAAAGCAACTTCG 301 CGGAGGCGCTGGCGGCCCACAAGTACCTGCTGGTGGAGTTCTATGCCCCTTGGTGTGGCC 361 ACTGCAAGGCTCTGGCCCCTGAGTATGCCAAAGCCGCTGGGAAGCTGAAGGCAGAAGGTT 421 CCGAGATCAGGTTGGCCAAGGTGGACGCCACGGAGGAGTCTGACCTGGCCCAGCAGTACG 481 GCGTGCGCGGCTATCCCACCATCAAGTTCTTCAGGAATGGAGACACGGCTTCCCCCAAGG 541 AATATACAGCTGGCAGAGAGGCTGATGACATCGTGAACTGGCTGAAGAAGCGCACGGGCC 601 CGGCTGCCACCACCCTGCCTGACGGCGCAGCTGCAGAGTCCTTGGTGGAGTCCAGCGAGG 661 TGGCTGTCATCGGCTTCTTCAAGGACGTGGAGTCGGACTCTGCCAAGCAGTTTTTGCAGG 721 CAGCAGAGGCCATCGATGACATACCATTTGGGATCACTTCCAACAGTGACGTGTTCTCCA 781 AATACCAGCTCGACAAAGATGGGGTTGTCCTCTTTAAGAAGTTTGATGAAGGCCGGAACA 841 ACTTTGAAGGGGAGGTCACCAAGGAGAACCTGCTGGACTTTATCAAACACAACCAGCTGC 901 CCCTTGTCATCGAGTTCACCGAGCAGACAGCCCCGAAGATTTTTGGAGGTGAAATCAAGA 961 CTCACATCCTGCTGTTCTTGCCCAAGAGTGTGTCTGACTATGACGGCAAACTGAGCAACT 1021 TCAAAACAGCAGCCGAGAGCTTCAAGGGCAAGATCCTGTTCATCTTCATCGACAGCGACC 1081 ACACCGACAACCAGCGCATCCTCGAGTTCTTTGGCCTGAAGAAGGAAGAGTGCCCGGCCG 1141 TGCGCCTCATCACCCTGGAGGAGGAGATGACCAAGTACAAGCCCGAATCGGAGGAGCTGA 1201 CGGCAGAGAGGATCACAGAGTTCTGCCACCGCTTCCTGGAGGGCAAAATCAAGCCCCACC 1261 TGATGAGCCAGGAGCTGCCGGAGGACTGGGACAAGCAGCCTGTCAAGGTGCTTGTTGGGA 1321 AGAACTTTGAAGACGTGGCTTTTGATGAGAAAAAAAACGTCTTTGTGGAGTTCTATGCCC 1381 CATGGTGTGGTCACTGCAAACAGTTGGCTCCCATTTGGGATAAACTGGGAGAGACGTACA 1441 AGGACCATGAGAACATCGTCATCGCCAAGATGGACTCGACTGCCAACGAGGTGGAGGCCG 1501 TCAAAGTGCACAGCTTCCCCACACTCAAGTTCTTTCCTGCCAGTGCCGACAGGACGGTCA 1561 TTGATTACAACGGGGAACGCACGCTGGATGGTTTTAAGAAATTCCTGGAGAGCGGTGGCC 1621 AGGATGGGGCAGGGGATGATGACGATCTCGAGGACCTGGAAGAAGCAGAGGAGCCAGACA 1681 TGGAGGAAGACGATGATCAGAAAGCTGTGAAAGATGAACTGTAATACGCAAAGCCAGACC 1741 CGGGCGCTGCCGAGACCCCTCGGGGGCTGCACACCCAGCAGCAGCGCACGCCTCCGAAGC 1801 CTGCGGCCTCGCTTGAAGGAGGGCGTCGCCGGAAACCCAGGGAACCTCTCTGAAGTGACA 1861 CCTCACCCCTACACACCGTCCGTTCACCCCCGTCTCTTCCTTCTGCTTTTCGGTTTTTGG 1921 AAAGGGATCCATCTCCAGGCAGCCCACCCTGGTGGGGCTTGTTTCCTGAAACCATGATGT 1981 ACTTTTTCATACATGAGTCTGTCCAGAGTGCTTGCTACCGTGTTCGGAGTCTCGCTGCCT 2041 CCCTCCCGCGGGAGGTTTCTCCTCTTTTTGAAAATTCCGTCTGTGGGATTTTTAGACATT 2101 TTTCGACATCAGGGTATTTGTTCCACCTTGGCCAGGCCTCCTCGGAGAAGCTTGTCCCCC 2161 GTGTGGGAGGGACGGAGCCGGACTGGACATGGTCACTCAGTACCGCCTGCAGTGTCGCCA 2221 TGACTGATCATGGCTCTTGCATTTTTGGGTAAATGGAGACTTCCGGATCCTGTCAGGGTG 2281 TCCCCCATGCCTGGAAGAGGAGCTGGTGGCTGCCAGCCCTGGGGCCCGGCACAGGCCTGG 2341 GCCTTCCCCTTCCCTCAAGCCAGGGCTCCTCCTCCTGTCGTGGGCTCATTGTGACCACTG 2401 GCCTCTCTACAGCACGGCCTGTGGCCTGTTCAAGGCAGAACCACGACCCTTGACTCCCGG 2461 GTGGGGAGGTGGCCAAGGATGCTGGAGCTGAATCAGACGCTGACAGTTCTTCAGGCATTT 2521 CTATTTCACAATCGAATTGAACACATTGGCCAAATAAAGTTGAAATTTTACCACCTGT

[0564] The start and stop codons are indicated in bold as well as the position corresponding to the microarray probe.

[0565] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000327801 and has a sequence as in SEQ ID NO:246

TABLE-US-00053 1 MLRRALLCLAVAALVRADAPEEEDHVLVLRKSNFAEALAAHKYLLVEFYAPWCGHCKALA 61 PEYAKAAGKLKAEGSEIRLAKVDATEESDLAQQYGVRGYPTIKFFRNGDTASPKEYTAGR 121 EADDIVNWLKKRTGPAATTLPDGAAAESLVESSEVAVIGFFKDVESDSAKQFLQAAEAID 181 DIPFGITSNSDVESKYQLDKDGVVLEKKEDEGRNNFEGEVTKENLLDFIKHNQLPLVIEF 241 TEQTAPKIFGGEIKTHILLFLPKSVSDYDGKLSNFKTAAESFKGKILFIFIDSDHTDNQR 301 ILEFFGLKKEECPAVRLITLEEEMTKYKPESEELTAERITEFCHRFLEGKIKPHLMSQEL 361 PEDWDKQPVKVLVGKNFEDVAFDEKKNVEVEFYAPWCGHCKQLAPIWDKLGETYKDHENI 421 VIAKMDSTANEVEAVKVHSFPTLKFFPASADRTVIDYNGERTLDGFKKFLESGGQDGAGD 481 DDDLEDLEEAEEPDMEEDDDQKAVKDEL

[0566] Primers for amplifying the sequence P4HB can be designed using primer design software such as Oligo Calc and/or Primer 3.

[0567] Examples of primer pairs for amplifying P4HB include those in

TABLE-US-00054 Forward SEQ ID NO: 247: GCTGCGGAAAAGCAACTTC Reverse SEQ ID NO: 248 CTGATCTCGGAACCTTCTGC Forward SEQ ID NO: 249 GGCTATCCCACCATCAAGTT Reverse SEQ ID NO: 250 TCTTCAGCCAGTTCACGATG Forward SEQ ID NO: 251 GCAGAGTCCTTGGTGGAGTC Reverse SEQ ID NO: 252 TGGAAGTGATCCCAAATGGT Forward SEQ ID NO: 253 ACCATTTGGGATCACTTCCA Reverse SEQ ID NO: 254 GGTGACCTCCCCTTCAAAGT Forward SEQ ID NO: 255 CCCCTTGTCATCGAGTTCAC Reverse SEQ ID NO: 256 TGCTCAGTTTGCCGTCATAG Forward SEQ ID NO: 257 TCACATCCTGCTGTTCTTGC Reverse SEQ ID NO: 258 GTCGCTGTCGATGAAGATGA Forward SEQ ID NO: 259 GACGGCAGAGAGGATCACAG Reverse SEQ ID NO: 260 TTCTTCCCAACAAGCACCTT Forward SEQ ID NO: 261 AGCCTGTCAAGGTGCTTGTT Reverse SEQ ID NO: 262 CAAATGGGAGCCAACTGTTT Forward SEQ ID NO: 263 ACAGCTTCCCCACACTCAAG Reverse SEQ ID NO: 264 CACCGCTCTCCAGGAATTT Forward SEQ ID NO: 265 GCACGCTGGATGGTTTTAAG Reverse SEQ ID NO: 266 TCATCGTCTTCCTCCATGTCT

[0568] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0569] Probes for detecting P4HB can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

TABLE-US-00055 SEQ ID NO: 267 CACAAGTACCTGCTGGTGGA SEQ ID NO: 268 GGCTTCCCCCAAGGAATATA SEQ ID NO: 269 GCTTCTTCAAGGACGTGGAG SEQ ID NO: 270 CTCGACAAAGATGGGGTTGT SEQ ID NO: 271 TCACATCCTGCTGTTCTTGC SEQ ID NO: 272 CTATGACGGCAAACTGAGCA SEQ ID NO: 273 AAAATCAAGCCCCACCTGAT SEQ ID NO: 274 TGAAGACGTGGCTTTTGATG SEQ ID NO: 275 GGTCATTGATTACAACGGGG SEQ ID NO: 276 ATGACGATCTCGAGGACCTG

[0570] A probe for detecting a P4HB nucleic acid that was used on the microarray has a sequence as in

TABLE-US-00056 SEQ ID NO: 277 GGCATTTCTATTTCACAATCGAATTGAACACATTGGCCAAATAAAGTT GAAATTTTCCCC

[0571] Other probes to P4HB are known in the art and/or can be readily designed by the skilled artisan.

[0572] Antibodies against P4HB include, but are not limited to, anti P4HB Cat# ab31811 de abcam (rabbit polyclonal) against residues 400 to 500; and PDI (P4HB) Mouse anti-Human Monoclonal Antibody from Lifespan Biosciences Cat# LS-C38385.

Example 16

P2RX4

[0573] P2RX4 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that P2RX4 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue as described in Example 2. It was surprisingly found that P2RX4 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that P2RX4 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0574] P2RX4

(also known as P2X4; P2X4R; P2RX4) P2X purinoceptor 4 (P2X4)(ATP receptor)(Purinergic receptor

[0575] ENSG00000135124

[0576] The sequence of an mRNA corresponding to P2RX4 is given in ENSEMBL accession no. ENST00000337233 and has a sequence as in SEQ ID NO:278

TABLE-US-00057 1 AAGTGCTGGGATGACAGGTGTGAGCCACCGCCCCCGGCCCCTCGCCCGCCTTTTGAAGGA 61 GCCTTTCGTCCTCAAGGGCGAGGCCACTCCCCCCCCGCGAGTTCCATGCCCCCTAGAGGG 121 TCATCGTTCCCGACGGGGAGGTGGCGCCCTCCCCCGGGCCCCGGGCCCCGACCGCCCGTG 181 CTGCCTCCTTCCGGGCCCTCCTCCGCGATGACGGCCGCCAGCAGGCCAGGCGGACTGG 241 GCGGGGCTCCGAGCGGGGACTGGGACCCAGACCGACTAGGGGACTGGGAGCGGGCGGCGC 301 GGCCATGGCGGGCTGCTGCGCCGCGCTGGCGGCCTTCCTGTTCGAGTACGACACGCCGCG 361 CATCGTGCTCATCCGCAGCCGCAAGTGGGGCTCATGAACCGCGCCGTGCAACTGCTCAT 421 CCTGGCCTACGTCATCGGGTGGGTGTTTGTGTGGGAAAAGGGCTACCAGGAAACTGACTC 481 CGTGGTCAGCTCCGTTACGACCAAGGTCAAGGGCGTGGCTGTGACCAACACTTCTAAACT 541 TGGATTCCGGATCTGGGATGTGGCGGATTATGTGATACCAGCTCAGGAGGAAAACTCCCT 601 CTTCGTCATGACCAACGTGATCCTCACCATGAACCAGACACAGGGCCTGTGCCCCGAGAT 661 TCCAGATGCGACCACTGTGTGTAAATCAGATGCCAGCTGTACTGCCGGCTCTGCCGGCAC 721 CCACAGCAACGGAGTCTCAACAGGCAGGTGCGTAGCTTTCAACGGGTCTGTCAAGACGTG 781 TGAGGTGGCGGCCTGGTGCCCGGTGGAGGATGACACACACGTGCCACAACCTGCTTTTTT 841 AAAGGCTGCAGAAAACTTCACTCTTTTGGTTAAGAACAACATCTGGTATCCCAAATTTAA 901 TTTCAGCAAGAGGAATATCCTTCCCAACATCACCACTACTTACCTCAAGTCGTGCATTTA 961 TGATGCTAAAACAGATCCCTTCTGCCCCATATTCCGTCTTGGCAAAATAGTGGAGAACGC 1021 AGGACACAGTTTCCAGGACATGGCCGTGGAGGGAGGCATCATGGGCATCCAGGTCAACTG 1081 GGACTGCAACCTGGACAGAGCCGCCTCCCTCTGCTTGCCCAGGTACTCCTTCCGCCGCCT 1141 CGATACACGGGACGTTGAGCACAACGTATCTCCTGGCTACAATTTCAGGTTTGCCAAGTA 1201 CTACAGAGACCTGGCTGGCAACGAGCAGCGCACGCTCATCAAGGCCTATGGCATCCGCTT 1261 CGACATCATTGTGTTTGGGAAGGCAGGGAAATTTGACATCATCCCCACTATGATCAACAT 1321 CGGCTCTGGCCTGGCACTGCTAGGCATGGCGACCGTGCTGTGTGACATCATAGTCCTCTA 1381 CTGCATGAAGAAAAGACTCTACTATCGGGAGAAGAAATATAAATATGTGGAAGATTACGA 1441 GCAGGGTCTTGCTAGTGAGCTGGACCAGTGAGGCCTACCCCACACCTGGGCTCTCCACAG 1501 CCCCATCAAAGAACAGAGAGGAGGAGGAGGGAGAAATGGCCACCACATCACCCCAGAGAA 1561 ATTTCTGGAATCTGATTGAGTCTCCACTCCACAAGCACTCAGGGTTCCCCAGCAGCTCCT 1621 GTGTGTTGTGTGCAGGATCTGTTTGCCCACTCGGCCCAGGAGGTCAGCAGTCTGTTCTTG 1681 GCTGGGTCAACTCTGCTTTTCCCGCAACCTGGGGTTGTCGGGGGAGCGCTGGCCCGACGC 1741 AGTGGCACTGCTGTGGCTTTCAGGGCTGGAGCTGGTTTGCTCAGAAGCCTCCTGTCTCC 1801 AGCTCTCTCCAGACAGGCCCAGTCCTCTGAGGCACGGCGGCTCTGTTCAAGCACTTTAT 1861 GCGGCAGGGAGGCCGCCTGGCTGCAGTCACTAGACTTGTAGCAGGCCTGGGCTGCAGGC 1921 TTCCCCCCGACCATTCCCTGCAGCCATGCGGAGAGCTGGCATTTCTCCTCAGAGAAGCG 1981 CTGTGCTAAGGTGATCGAGGACCAGACATTAAAGCGTGATTTTCTT

[0577] The start and stop codons are indicated in bold as well as the position corresponding to the microarray probe.

[0578] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000336607 and has a sequence as in SEQ ID NO:279

TABLE-US-00058 1 MAGCCAALAFLFEYDTPRIVLIRSRKVGLMNRAVQLLILAYVIGWVFVWEKGYQETDSV 61 VSSVTTKVKGVAVTNTSKLGFRIWDVADYVIPAQEENSLFVMTNVILTMNQTGGLCPEIP 121 DATTVCKSDASCTAGSAGTHSNGVSTGRCVAFNGSVKTCEVAAWCPVEDDTHVPQPAFLK 181 AAENFTLLVKNNIWYPKFNFSKRNILPNITTTYLKSCIYDAKATDPFCPIFRLGKIVENAG 241 HSFQDMAVEGGIMGIQVNWDCNLDRAASLCLPPYSFRRLDTRDVEHNVSPGYNFRFAKYY 301 RDLAGNEQRTLIKAYGIRFDIIVFGKAGKDIIPTMINIGSGLALLGMATVLCDIIVLYC 361 MKKRLYYREKKYKYVEDYEQGLASELDQ ENST00000359949 ENSP00000353032 SEQ ID NO: 280 1 MAGCCAALAFLFEYDTPRIVLIRSRKVGLMNRAVQLLILAYVIGWVFVWEKGYQETDSV 61 VSSVTTKVKGVAVTNTSKLGFRIWDVADYVIPAQEENSLFVMTNVILTMNQTGGLCPEIP 121 DATTVCKSDASCTAGSAGTHSNVVCTLIPAFLKAAENFTLLVKNNIWYPKFNFSKRNILP 181 NITTTYLKSCIYDAKTDPFCPIFRLGKIVENAGHSFQDMAVDGGIMGIQVNWDCNLDRAA 241 SLCLPRYSFRRLDTRDVEHNVSPGYNFRFAKYYRDLAGNEQRTKIKAYGIRFDIIVFGKA 301 GKFDIIPTMINIGSGLALLGMATVLCDIIVLYCMKKRLYYREKKYKYVEDYEQGLASELD 361 Q

[0579] Examples of primer pairs for amplifying P2RX4 include:

TABLE-US-00059 Forward SEQ ID NO: 281 AACTGCTCATCCTGGCCTAC Reverse SEQ ID NO: 282 GTCGTAACGGAGCTGACCAC Forward SEQ ID NO: 283 GGATGTGGCGGATTATGTG Reverse SEQ ID NO: 284 CCTGTGTCTGGTTCATGGTG Forward SEQ ID NO: 285 AGATTCCAGATGCGACCACT Reverse SEQ ID NO: 286 CAGACCCGTTGAAAGCTACG Forward SEQ ID NO: 287 TCTGTCAAGACGTGTGAGGTG Reverse SEQ ID NO: 288 CCAAAAGAGTGAAGTTTTCTGC Forward SEQ ID NO: 289 TTTTGGTTAAGAACAACATCTGG Reverse SEQ ID NO: 290 ATATGGGGCAGAAGGGATCT Forward SEQ ID NO: 291 CGCTTCGACATCATTGTGTT Reverse SEQ ID NO: 292 TAGCAGTGCCAGGCCAGAG Forward SEQ ID NO: 293 GAAAAGACTCTACTATCGGGAGAA Reverse SEQ ID NO: 294 CTGTTCTTTGATGGGGCTGT

[0580] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0581] Probes for detecting P2RX4 derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents).

[0582] Other examples of probes include:

TABLE-US-00060 SEQ ID NO: 295 TTGTGTGGGAAAAGGGCTAC SEQ ID NO: 296 TTCGTCATGACCAACGTGAT SEQ ID NO: 297 TCAGATGCCAGCTGTACTGC SEQ ID NO: 298 GTGGAGGATGACACACACGT SEQ ID NO: 299 TCCTTCCCAACATCACCACT SEQ ID NO: 300 GAAGGCAGGGAAATTTGACA SEQ ID NO: 301 GGGTCTTGCTAGTGAGCTGG

[0583] A probe for detecting a P2RX4 nucleic acid that was used on the microarray has a sequence as in

TABLE-US-00061 SEQ ID NO: 302 CTCCTCAGAGAAGCGCTGTGCTAAGGTGATCGAGGACCAGACATTAAAG CGTGATTTTCT

[0584] Other probes to P2RX4 are known in the art and/or can be readily designed by the skilled artisan.

[0585] Antibodies to P2RX4, include, but are not limited to, Mouse Anti-Human P2RX4 Maxpab polyclonal, unconjugated from Novus Biologicals, P2RX4 (1 a.a. .about.388 a.a) full-length human protein, H00005025-B01, and Goat Anti-P2RX4 polyclonal, unconjugated from Novus Biologicals, NBP1-00141, Synthetic peptide, SEQ ID NO:303 YREKKYKYVEDYEQ, representing the C Terminus of the sequence according to NP.sub.--002551.2

Example 17

PPFIBP2

[0586] PPFIBP2 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that PPFIBP2 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue as described in Example 2. It was surprisingly found that PPFIBP2 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that PPFIBP2 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0587] PPPFIBP2

[0588] The sequence of an mRNA corresponding to PPPFIBP2 is given in ENSEMBL accession no. ENST00000299492 and has a sequence as in SEQ ID NO:304

TABLE-US-00062 1 GCAGGCTTCTTCGGTGCCCGAGAGGGAGCGGGTGCCCAAGGGGGTGGTCCCTGTGGCAGG 61 TCCCGGGGTGGGGGCGCGGCGCTCCGGGAAGAGCCTTCCGCAGGTCCCCGCCCCGTCACG 121 TGGGCGCCGGCCCCGGCCGCTGCGGTCGGTCCGCTGGTTGGTCGGGCGCTTGGTCCGGCA 181 GTTGGTCGGTGGGCCAGTGGCCCGTCGCTCGCTTCTGGGCTCTCATGTTTGAAGGTGGGA 241 GGGACACGGGAGCGGCCCGCACACCTGAGCCGCCCGGAGAGGAGCCTCGGCCCCGTACCC 301 AGTAAGAAGAGGAGGAGGCCAGGCAGGCAAAAGGAGTCATGGCTTCTGATGCTAGTCATG 361 CGCTGGAAGCTGCCCTGGAGCAAATGGACGGGATCATTGCAGGCACTAAAACAGGTGCAG 421 ATCTTAGTGATGGTACTTGTGAGCCTGGACTGGCTTCCCCGGCCTCCTACATGAACCCCT 481 TCCCGGTGCTCCATCTCATCGAGGACTTGAGGCTGGCCTTGGAGATGCTGGAGCTTCCTC 541 AGGAGAGAGCAGCCCTCCTGAGCCAGATCCCTGGCCCAACAGCTGCCTACATAAAGGAAT 601 GGTTTGAAGAGAGCTTGTCCCAGGTAAACCACCACAGTGCTGCTAGTAATGAAACCTACC 661 AGGAACGCTTGGCACGTCTAGAAGGGGATAAGGAGTCCCTCATATTGCAGGTGAGTGTCC 721 TCACAGACCAAGTAGAAGCCCAGGGAGAAAAGATTCGAGACCTGGAAGTGTGTCTGGAAG 781 GACACCAGGTGAAACTCAATGCTGCTGAAGAGATGCTTCAACAGGAGCTGCTAAGCCGCA 841 CATCTCTTGAGACCCAGAAGCTCGATCTGATGACTGAAGTGTCTGAGCTGAAGCTCAAGC 901 TGGTTGGCATGGAGAAGGAGCAGAGAGAGCAGGAGGAGAAGCAGAGAAAAGCAGAGGAGT 961 TACTGCAAGAGCTCAGGCACCTCAAAATCAAAGTGGAAGAGTTGGAAAATGAAAGGAATC 1021 AGTATGAATGGAAGCTAAAGGCCACTAAGGCTGAAGTCGCCCAGCTGCAAGAACAGGTGG 1081 CCCTGAAAGATGCAGAAATTGAGCGTCTGCACAGCCAGCTCTCCCGGACAGCAGCTCTCC 1141 ACAGTGAGAGTCACACAGAGAGAGACCAAGAAATTCAACGTCTGAAAATGGGGATGGAAA 1201 CTTTGCTGCTTGCCAATGAAGATAAGGACCGTCGGATAGAGGAGCTTACGGGGCTGTTAA 1261 ACCAGTACCGGAAGGTAAAGGAGATTGTGATGGTCACTCAAGGGCCTTCGGAGAGAACTC 1321 TCTCAATCAATGAAGAAGAACCGGAGGGAGGTTTCAGCAAGTGGAACGCTACAAATAAGG 1381 ACCCTGAAGAATTATTTAAACAAGAGATGCCTCCAAGATGTAGCTCTCCTACAGTGGGGC 1441 CACCTCCATTGCCACAGAAATCACTGGAAACCAGGGCTCAGAAAAAGCTCTCTTGTAGTC 1501 TAGAAGACTTGAGAAGTGAATCTGTGGATAAGTGTATGGATGGGAACCAGCCCTTCCCGG 1561 TGTTAGAACCCAAGGACAGCCCTTTCTTGGCGGAGCACAAATATCCCACTTTACCTGGGA 1621 AGCTTTCAGGAGCCACGCCCAATGGAGAGGCTGCCAAATCTCCTCCCACCATCTGCCAGC 1681 CTGACGCCACGGGGAGCAGCCTGCTGAGGCTGAGAGACACAGAAAGTGGCTGGGACGACA 1741 CTGCTGTGGTCAATGACCTCTCATCCACATCATCGGGCACTGAATCAGGTCCTCAGTCTC 1801 CTCTGACACCAGATGGTAAACGGAATCCCAAAGGCATTAAGAAGTTCTGGGGAAAAATCC 1861 GAAGAACTCAGTCAGGAAATTTCTACACTGACACGCTGGGGATGGCAGAGTTTCGACGAG 1921 GTGGGCTCCGGGCAACCGCAGGGCCAAGACTCTCTAGGACCAGGGACTCCAAGGGACAGA 1981 AAAGTGACGCCAATGCCCCCTTTGCCCAGTGGAGCACAGAGCGTGTGTGTGCATGGCTGG 2041 AGGACTTTGGCCTGGCTCAGTATGTGATCTTTGCCAGGCAGTGGGTATCTTCTGGCCACA 2101 CCTTATTGACAGCCACCCCTCAGGACATGGAAAAGGAGCTAGGAATTAAGCACCCACTCC 2161 ACAGGAAGAAGCTTGTTTTAGCAGTGAAAGCCATCAACACCAAACAGGAGGAGAAGTCTG 2221 CACTGCTAGACCACATTTGGGTGACAAGGTGGCTTGATGATATTGGCTTACCCCAGTACA 2281 AAGACCAGTTTCATGAATCTAGAGTTGACAGACGAATGCTGCAATACCTAACTGTGAACG 2341 ATTTACTCTTCTTAAAAGTCACCAGCCAACTACATCATCTCAGCATCAAATGTGCCATTC 2401 ACGTGCTGCATGTCAACAAGTTCAACCCCCACTGCCTGCACCGGCGGCCAGCTGATGAGA 2461 GTAACCTTTCTCCTTCAGAAGTTGTACAGTGGTCCAACCACAGGGTGATGGAGTGGTTAC 2521 GATCTGTGGACCTGGCAGAGTATGCACCCAATCTTCGAGGGAGTGGAGTCCATGGAGGCC 2581 TCATTATCCTGGAGCCACGCTTCACTGGGGACACCCTGGCTATGCTTCTCAACATCCCCC 2641 CACAAAAGACGCTCCTCAGGCGCCACCTGACCACCAAGTTCAATGCCTTGATTGGTCCGG 2701 AGGCTGAACAGGAGAAGCGAGAGAAAATGGCCTCACCAGCTTACACACCACTGACCACCA 2761 CAGCCAAAGTCCGGCCAAGGAAACTAGGATTTTCACACTTCGGAAACATAAGAAAAAAGA 2821 AGTTCGATGAATCGACGGACTACATTTGCCCAATGGAGCCCAGTGACGGTGTCAGTGATA 2881 GTCACAGGGTCTACAGTGGCTACCGGGGCCTCAGCCCCCTTGATGCCCCTGAACTGGATG 2941 GGCTGGACCAGGTGGGACAGATTAGCTGATGCCCTTGTCACCTGCCCTCTGTGCACCCTG 3001 AGAGCTCACAGTAACACTGTGTGTGTCACCATATAACTGCACCTCACCCCCGCACGTGTG 3061 CATGACTCGCAGAGAATATTCCAGCAATTGTGTACCCCTGGGCCAGTCTCTTTGAACCCT 3121 GAGGGTGGCCAGGATCTGGAGCTGCATCTCTAAGGGGCCAGGCTTTGGGGACCATTGCCA 3181 AAGGTGGACTCAGGAGGAAAGACACTTAAAGACACTTTTACATGTCTAGTAATTCTTGAT 3241 GTTCATCTTCAGCACCAGTGGAAACACATGAACTTCGATGCAGGTCCAGAGACCATGGAC 3301 ACTCCCACGAGGCTCAGCTCTCAGGCACCCCCTACACTTCAGTTGAGGGAAAAGCTCAAG 3361 TGCCTTAGGCCCGTGGACCACAGTCTTGGCTGAGATCAAAGGGATGAGCAACAGGGACTT 3421 CTGCCACAGTGACAATGGAATTGTGTTGTGCCTTACTTCAGAGGTGGTCTCTTCTTTCTT 3481 GTAATAAAAGCAATATTTATGC

[0589] The start and stop codons are indicated in bold as well as the position corresponding to the microarray probe.

[0590] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000299492 and has a sequence as in SEQ ID NO:305

TABLE-US-00063 1 MASDASHALEAALEQMDGIIAGTKTGADLSDGTCEPGLASPASYMNPFPVLHLIEDLRLA 61 LEMLELPQERAALLSQIPGPTAAYIKEWFEESLSQVNHHSAASNETYQERLARLEGDKES 121 LILQVSVLTDQVEAQGEKIRDLEVCLEGHQVKLNAAEEMLQQELLSRTSLETQKLDLMTE 181 VSELKLKLVGMEKEQREQEEKQRKAEELLQELRHLKIKVEELENERNQYEWKLKATKAEV 241 AQLQEQVALKDAEIERLHSQLSRTAALHSESHTERDQEIQRLKMGMETLLLANEDKDRRI 301 EELTGLLNQYRKVKEIVMVTQGPSERTLSINEEEPEGGFSKWNATNKDPEELFKQEMPPR 361 CSSPTVGPPPLPQKSLETRAQKKLSCSLEDLRSESVDKCMDGNQPFPVLEPKDSPFLAEH 421 KYPTLPGKLSGATPNGEAAKSPPTICQPDATGSSLLRLRDTESGWDDTAVVNDLSSTSSG 481 TESGPQSPLTPDGKRNPKGIKKFWGKIRRTQSGNFYTDTLGMAEFRRGGLRATAGPRLSR 541 TRDSKGQKSDANAPFAQWSTERVCAWLEDFGLAQYVIFARQWVSSGHTLLTATPQDMEKE 601 LGIKHPLHRKKLVLAVKAINTKQEEKSALLDHIWVTRWLDDIGLPQYKDQFHESRVDRRM 661 LQYLTVNDLLFLKVTSQLHHLSIKCAIHVLHVNKFNPHCLHRRPADESNLSPSEVVQWSN 721 HRVMEWLRSVDLAEYAPNLRGSGVHGGLIILEPRFTGDTLAMLLNIPPQKTLLRRHLTTK 781 FNALIGPEAEQEKREKMASPAYTPLTTTAKVRPRKLGFSHFGNIRKKKFDESTDYICPME 841 PSDGVSDSHRVYSGYRGLSPLDAPELDGLDQVGQIS

[0591] Primers for amplifying the sequence ENST00000299492 can be designed using primer design software such as Oligo Calc and/or Primer 3.

[0592] Examples of primer pairs for amplifying PPFIBP2 include:

TABLE-US-00064 1) Forward SEQ ID NO: 306 GCTAGTCATGCGCTGGAAG Reverse SEQ ID NO: 307 GAAGCTCCAGCATCTCCAAG 2) Forward SEQ ID NO: 308 CCCAGGTAAACCACCACAGT Reverse SEQ ID NO: 309 CTGGTGTCCTTCCAGACACA 3) Forward SEQ ID NO: 310 TGTGTCTGGAAGGACACCAG Reverse SEQ ID NO: 311 TCCTCCTGCTCTCTCTGCTC 4) Forward SEQ ID NO: 312 AAGAGCTCAGGCACCTCAAA Reverse SEQ ID NO: 313 CTCACTGTGGAGAGCTGCTG 5) Forward SEQ ID NO: 314 AAACTTTGCTGCTTGCCAAT Reverse SEQ ID NO: 315 TTGAGTGACCATCACAATCTCC 6) Forward SEQ ID NO: 316 TCTCTCAATCAATGAAGAAGAACC Reverse SEQ ID NO: 317 TCCAGTGATTTCTGTGGCAAT 7) Forward SEQ ID NO: 318 GCCTCCAAGATGTAGCTCTCC Reverse SEQ ID NO: 319 TCCACAGATTCACTTCTCAAGTC 8) Forward SEQ ID NO: 320 CGGAGCACAAATATCCCACT Reverse SEQ ID NO: 321 CTTTGGGATTCCGTTTACCA 9) Forward SEQ ID NO: 322 TGGTAAACGGAATCCCAAAG Reverse SEQ ID NO: 323 TTGGAGTCCCTGGTCCTAGA 10) Forward SEQ ID NO: 324 TCTAGGACCAGGGACTCCAA Reverse SEQ ID NO: 325 GGGTGGCTGTCAATAAGGTG

[0593] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0594] Probes for detecting PPFIBP2 derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents).

[0595] Other examples of probes include:

[0596] Probe:

TABLE-US-00065 SEQ ID NO: 326 CAGGCACTAAAACAGGTGCA SEQ ID NO: 327 AGGGGATAAGGAGTCCCTCA SEQ ID NO: 328 TTGAGACCCAGAAGCTCGAT SEQ ID NO: 329 GAAATTGAGCGTCTGCACAG SEQ ID NO: 330 TTACGGGGCTGTTAAACCAG SEQ ID NO: 331 CAGCAAGTGGAACGCTACAA SEQ ID NO: 332 TGCCACAGAAATCACTGGAA SEQ ID NO: 333 ACACAGAAAGTGGCTGGGAC SEQ ID NO: 334 TTCTACACTGACACGCTGGG SEQ ID NO: 335 GGCCTGGCTCAGTATGTGAT

[0597] A probe for detecting PPFIBP2 nucleic acid that was used on the microarray has a sequence as in

TABLE-US-00066 SEQ ID NO: 336 AGATCAAAGGGATGAGCAACAGGGACTTCTGCCACAGTGACAATGGAATT GTGTTGTGCC

[0598] Other probes to PPP1R16A are known in the art and/or can be readily designed by the skilled artisan. [0599] 1) Antibodies: [0600] 2) Mouse Anti-Human PPFIBP2 Monoclonal Antibody, Unconjugated, Clone 3A5, Abnova Corporation, PPFIBP2 (NP.sub.--003612, 1 a.a. .about.101 a.a) partial recombinant protein with GST tag. MW of the GST tag alone is 26 KDa. [0601] 3) Rabbit Anti-Human PPFIBP2 Purified--MaxPab Polyclonal Antibody, Unconjugated, Abnova Corporation, PPFIBP2 (NP.sub.--003612.1, 1 a.a. .about.876 a.a) full-length human protein.

Example 18

PPP1R16A

[0602] PPP1R16A (protein phosphatase 1, regulatory (inhibitor) subunit 16A) also known as MGC14333 and MYPT3 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that PPP1R16A was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue as described in Example 2. It was surprisingly found that PPP1R16A was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that PPP1R16A can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0603] PPP1R16A, also named Myosin phosphatase targeting subunit 3 (MYPT3) is a membrane located protein which having 524 amino acid residues, in which five Ankyrin repeats and a consensus PP1 binding site are located within the N-terminal 300 amino acid residues. The C-terminal region with 224 residues contains two possible Src homology 3 binding sites and a prenylation motif (CaaX). These structural features suggest that R16A could be a scaffold protein regulating protein-protein interactions as well as cellular signalling. (PMID: 18202305)

[0604] The sequence of an mRNA corresponding to PPP1R16A is given in ENSEMBL accession no. ENST00000292539 and has a sequence as in SEQ ID NO:337

TABLE-US-00067 GTGAAAAGAGGACTCTCAGGGGCTCACAGGGGCTCTCACTGCTGGTTGGC CCTGCCCTCCCTTCCCCCTCAGCAGGGTGCCCGGAAGCTGGAACCTTGTT ATCTGGGTAATTAGTTTCAGACCCTGCACTGAGGCCGGCCAGGTCTCGGG GCTGCCTCCCATAGGTTGTGCACCCTGACCCCGAGAGGGAGGCGAGGCGC TGCTTGTCGACAGCTAGAGGCTGGCCTGGGGAGCAGGTTTGGGGTGCCCT CCCACACTGCCCTCCCTGCCCCGGCCCATGCCCCCCAGGGCTGCCTGGGC CTGGTTATTGTGTGGGGCCTCCTGACCCAGCCAAGGGCACGAAGCTCTGG GAAGGGGATGCCCCCGAGGGTGCCAGTCCAGCTAGCTGCCCCACCCCTCA GGCCCAGCCTGGCCCCCAAGCTCCCCACTCTGGTGCCCCGAGCAGCCCTG TGGGCAAGCAGCCGCCGCCATGGCCGAGCACCTGGAGCTGCTGGCAGAGA TGCCCATGGTGGGCAGGATGAGCACACAGGAGCGGCTGAAGCATGCCCAG AAGCGGCGCGCCCAGCAGGTGAAGATGTGGGCCCAGGCTGAGAAGGAGGC CCAGGGCAAGAAGGGTCCTGGGGAGCGTCCCCGGAAGGAGGCAGCCAGCC AAGGGCTCCTGAAGCAGGTCCTCTTCCCTCCCAGTGTTGTCCTTCTGGAG GCCGCTGCCCGAAATGACCTGGAAGAAGTCCGCCAGTTCCTTGGGAGTGG GGTCAGCCCTGACTTGGCCAACGAGGACGGCCTGACGGCCCTGCACCAGT GCTGCATTGATGATTTCCGAGAGATGGTGCAGCAGCTCCTGGAGGCTGGG GCCAACATCAATGCCTGTGACAGTGAGTGCTGGACGCCTCTGCATGCTGC GGCCACCTGCGGCCACCTGCACCTGGTGGAGCTGCTCATCGCCAGTGGCG CCAATCTCCTGGCGGTCAACACCGACGGGAACATGCCCTATGACCTGTGT GATGATGAGCAGACGCTGGACTGCCTGGAGACTGCCATGGCCGACCGTGG CATCACCCAGGACAGCATCGAGGCCGCCCGGGCCGTGCCAGAACTGCGCA TGCTGGACGACATCCGGAGCCGGCTGCAGGCCGGGGCAGACCTCCATGCC CCCCTGGACCACGGGGCCACGCTGCTGCACGTCGCAGCCGCCAACGGGTT CAGCGAGGCGGCTGCCCTGCTGCTGGAACACCGAGCCAGCCTGAGCGCTA AGGACCAAGACGGCTGGGAGCCGCTGCACGCCGCGGCCTACTGGGGCCAG GTGCCCCTGGTGGAGCTGCTCGTGGCGCACGGGGCCGACCTGAACGCAAA GTCCCTGATGGACGAGACGCCCCTTGATGTGTGCGGGGACGAGGAGGTGC GGGCCAAGCTGCTGGAGCTGAAGCACAAGCACGACGCCCTCCTGCGCGCC CAGAGCCGCCAGCGCTCCTTGCTGCGCCGCCGCACCTCCAGCGCCGGCAG CCGCGGGAAGGTGGTGAGGCGGGTGAGCCTAACCCAGCGCACCGACCTGT ACCGCAAGCAGCACGCCCAGGAGGCCATCGTGTGGCAACAGCCGCCGCCC ACCAGCCCGGAGCCGCCCGAGGACAACGATGACCGCCAGACAGGCGCAGA GCTCAGGCCGCCGCCCCCGGAGGAGGACAACCCCGAAGTGGTCAGGCCGC ACAATGGCCGAGTAGGGGGCTCCCCAGTGCGGCATCTATACTCCAAGCGA CTAGACCGGAGTGTCTCCTACCAGCTGAGCCCCCTGGACAGCACCACCCC CCACACCCTGGTCCACGACAAGGCCCACCACACCCTGGCTGACCTGAAGC GCCAGCGAGCTGCTGCCAAGCTGCAGCGACCCCCACCTGAGGGGCCCGAG AGCCCTGAGACAGCTGAGCCTGGCCTGCCTGGTGACACGGTGACCCCCCA GCCTGACTGTGGCTTCAGGGCAGGCGGGGACCCACCCCTGCTCAAGCTCA CAGCCCCGGCGGTGGAGGCTCCCGTGGAGAGGAGGCCGTGCTGCCTGCTC ATGTGAGGCTGTTGCTCAGCATGCAGGGGCCCTGTCGCGGGCACAGCCCA AGGCTGCCTCCCCACGGTGCGTGCCCTGGTGCTGCGGGTGCAGCACGGAA ACCCCGGCTTCTACTGTACAGGACACTGGCCCCTCTCAGGTCAGAAGACA TGCCTGGAGGGATGTCTGGCTGCAAAGACTATTTTTATCCTGCAACTCTT GATAAAGGGCTGTTTTGCCATGGAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAA

[0605] The start and stop codons are indicated in bold as well as the position corresponding to the microarray probe.

[0606] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000292539 and has a sequence as in SEQ ID NO:338

TABLE-US-00068 MAEHLELLAEMPMVGRMSTQERLKHAQKRRAQQVKMWAQAEKEAQGKKGP GERPRKEAASQGLLKQVLFPPSVVLLEAAARNDLEEVRQFLGSGVSPDLA NEDGLTALHQCCIDDFREMVQQLLEAGANINACDSECWTPLHAAATCGHL HLVELLIASGANLLAVNTDGNMPYDLCDDEQTLDCLETAMADRGITQDSI EAARAVPELRMLDDIRSRLQAGADLHAPLDHGATLLHVAAANGFSEAAAL LLEHRASLSAKDQDGWEPLHAAAYWGQVPLVELLVAHGADLNAKSLMDET PLDVCGDEEVRAKLLELKHKHDALLRAQSRQRSLLRRRTSSAGSRGKVVR RVSLTQRTDLYRKQHAQEAIVWQQPPPTSPEPPEDNDDRQTGAELRPPPP EEDNPEVVRPHNGRVGGSPVRHLYSKRLDRSVSYQLSPLDSTTPHTLVHD KAHHTLADLKRQRAAAKLQRPPPEGPESPETAEPGLPGDTVTPQPDCGFR AGGDPPLLKLTAPAVEAPVERRPCCLLM

[0607] Primers for amplifying the sequence ENST00000292539 can be designed using primer design software such as Oligo Calc and/or Primer 3.

[0608] Examples of primer pairs for amplifying PPP1R16A include:

TABLE-US-00069 Forward SEQ ID NO: 339 GTGTTGTCCTTCTGGAGGCCG (Ex2) Reverse SEQ ID NO: 340 GCCGTCAGGCCGTCCTCGTTG (Ex3) Forward SEQ ID NO: 341 GCTGCCCGAAATGACCTGG (Ex3) Reverse SEQ ID NO: 342 CGGAAATCATCAATGCAGC (Ex5) Forward SEQ ID NO: 343 GACGCCTCTGCATGCTGCGG (Ex5) Reverse SEQ ID NO: 344 CACAGGTCATAGGGCATGTTC (Ex6) Forward SEQ ID NO: 345 GATGAGCAGACGCTGGACTG (Ex6) Reverse SEQ ID NO: 346 CTCCGGATGTCGTCCAGC (Ex7) Forward SEQ ID NO: 347 CAGGCCGGGGCAGACCTC Reverse SEQ ID NO: 348 GGCTCGGTGTTCCAGCAGCAG Forward SEQ ID NO: 349 GGGAGCCGCTGCACGCC Reverse SEQ ID NO: 350 CCCGCACCTCCTCGTCCC Forward SEQ ID NO: 351 CTGCGCGCCCAGAGCCGC Reverse SEQ ID NO: 352 GCGTGCTGCTTGCGGTAC Forward SEQ ID NO: 353 GCCAGACAGGCGCAGAGCTC Reverse SEQ ID NO: 354 CTACTCGGCCATTGTGCG

[0609] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0610] Probes for detecting PPP1R16A derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents).

[0611] Other examples of probes include:

TABLE-US-00070 SEQ ID NO: 355 TCTACTGTACAGGACACTGGCCCCTCTCAGGTCAGAAGACATGCCTGGAG GGATGTCTGGCTGCAAAGACTATTTTTATCC SEQ ID NO: 356 CTGACGGCCCTGCACCAGTGCTGCATTGATGATTTCC SEQ ID NO: 357 GACTGCCATGGCCGACCGTGGCATCACCCAG SEQ ID NO: 358 GCTCGTGGCGCACGGGGCCGACCTGAACGC SEQ ID NO: 359 GCGCCGGCAGCCGCGGGAAGGTGGTGAGG

[0612] Other probes to PPP1R16A are known in the art and/or can be readily designed by the skilled artisan.

[0613] Antibodies against PPP1R16A include, but are not limited to, Abnova Corporation Cat# H00084988-M06 which is a mouse monoclonal antibody raised against a partial recombinant PPP1R16A: 429 a.a. .about.529 a.a; and from Abnova Cat# H00084988-B01 which is a mouse polyclonal raised against a full-length human PPP1R16A protein.

Example 19

RASSF7

[0614] RASSF7, Ras association (RalGDS/AF-6) domain family (N-terminal) member 7 also known as 2400009B11RIK, AW210608, C11ORF13, HRAS1, HRC1, MGC126069, MGC126070, and RGD1306244 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that RASSF7 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue as described in Example 2. It was surprisingly found that RASSF7 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that RASSF7 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0615] RASSF7 is a member of a new Ras effector family characterise for the presence of a RA domain in their sequence. Although they interact either directly or indirectly with activated Ras, their role in mediating its biological effects remains unclear. What is clear is that they seem to modulate some of the growth inhibitory responses mediated by Ras and may serve as tumour suppressor genes. In fact, it is been described that members of the family are silenced in tumours by methylation of their promoters. (PMID: 17692468).

[0616] The sequence of an mRNA corresponding to RASSF7 is given in ENSEMBL accession no. ENST00000344375 and has a sequence as in SEQ ID NO:360

TABLE-US-00071 GAATTCGGGGGGAGGGGGCAGTGTCCTCCGAGCCAGGACAGGCATGTTGT TGGGACTGGCGGCCATGGAGCTGAAGGTGTGGGTGGATGGCATCCAGCGT GTGGTCTGTGGGGTCTCAGAGCAGACCACCTGCCAGGAAGTGGTCATCGC ACTAGCCCAAGCAATAGGCCAGACTGGCCGCTTTGTGCTTGTGCAGCGGC TTCGGGAGAAGGAGCGGCAGTTGCTGCCACAAGAGTGTCCAGTGGGCGCC CAGGCCACCTGCGGACAGTTTGCCAGCGATGTCCAGTTTGTCCTGAGGCG CACAGGGCCCAGCCTAGCTGGGAGGCCCTCCTCAGACAGCTGTCCACCCC CGGAACGCTGCCTAATTCGTGCCAGCCTCCCTGTAAAGCCACGGGCTGCG CTGGGCTGTGAGCCCCGCAAAACACTGACCCCCGAGCCAGCCCCCAGCCT CTCACGCCCTGGGCCTGCGGCCCCTGTGACACCCACACCAGGCTGCTGCA CAGACCTGCGGGGCCTGGAGCTCAGGGTGCAGAGGAATGCTGAGGAGCTG GGCCATGAGGCCTTCTGGGAGCAAGAGCTGCGCCGGGAGCAGGCCCGGGA GCGAGAGGGACAGGCACGCCTGCAGGCACTAAGTGCGGCCACTGCTGAGC ATGCCGCCCGGCTGCAGGCCCTGGACGCTCAGGCCCGTGCCCTGGAGGCT GAGCTGCAGCTGGCAGCGGAGGCCCCTGGGCCCCCCTCACCTATGGCATC TGCCACTGAGCGCCTGCACCAGGACCTGGCTGTTCAGGAGCGGCAGAGTG CGGAGGTGCAGGGCAGCCTGGCTCTGGTGAGCCGGGCCCTGGAGGCAGCA GAGCGAGCCTTGCAGGCTCAGGCTCAGGAGCTGGAGGAGCTGAACCGAGA GCTCCGTCAGTGCAACCTGCAGCAGTTCATCCAGCAGACCGGGGCTGCGC TGCCACCGCCCCCACGGCCTGACAGGGGCCCTCCTGGCACTCAGGGCCCT CTGCCTCCAGCCAGAGAGGAGTCCCTCCTGGGCGCTCCCTCTGAGTCCCA TGCTGGTGCCCAGCCTAGGCCCCGAGGTGGCCCCCATGACGCAGAACTCC TGGAGGTAGCAGCAGCTCCTGCCCCAGAGTGGTGTCCTCTGGCAGCCCAG CCCCAGGCTCTGTGACAGCCTAGTGAGGGCTGCAAGACCATCCTGCCCGG ACCACAGAAGGAGAGTTGGCGGTCACAGAGGGCTCCTCTGCCAGGCAGTG GGAAGCCCTGGGTTTGGCCTCAGGAGCTGGGGGTGCAGTGGGGGACTGCC CTAGTCCTTGCCAGGTCGCCCAGCACCCTGGAGAAGCATGGGGCGTAGCC AGCTCGGAACTTGCCAGGCCCCAAAGGCCACGACTGCCTGTTGGGGACAG GAGATGCATGGACAGTGTGCTCAAGCTGTGGGCATGTGCTTGCCTGCGGG AGAGGTCCTTCACTGTGTGTACACAGCAAGAGCATGTGTGTGCCACTTCC CCTACCCCAACGTGAAAACCTCAATAAACTGCCCGAAGC

[0617] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000344226 and has a sequence as in SEQ ID NO:361

TABLE-US-00072 MLLGLAAMELKVWVDGIQRVVCGVSEQTTCQEVVIALAQAIGQTGRFVLV QRLREKERQLLPQECPVGAQATCGQFASDVQFVLRRTGPSLAGRPSSDSC PPPERCLIRASLPVKPRAALGCEPRKTLTPEPAPSLSRPGPAAPVTPTPG CCTDLRGLELRVQRNAEELGHEAFWEQELRREQAREREGQARLQALSAAT AEHAARLQALDAQARALEAELQLAAEAPGPPSPMASATERLHQDLAVQER QSAEVQGSLALVSRALEAAERALQAQAQELEELNRELRQCNLQQFIQQTG AALPPPPRPDRGPPGTQGPLPPAREESLLGAPSESHAGAQPRPRGGPHDA ELLEVAAAPAPEWCPLAAQPQAL

[0618] Primers for amplifying the sequence ENST00000344375 can be designed using primer design software such as Oligo Calc and/or Primer 3.

[0619] Examples of primer pairs for amplifying RASSF7 include:

TABLE-US-00073 Forward SEQ ID NO: 362 CTGCCAGGAAGTGGTCAT C (Ex1) Reverse SEQ ID NO: 363 GCCGCTGCACAAGCACA (ex2) Forward SEQ ID NO: 364 CATGGAGCTGAAGGTG (ex1) Reverse SEQ ID NO: 365 CTCAGGACAAACTGGAC (ex2) Forward SEQ ID NO: 366 GCCACTGAGCGCCTGC (Ex2) Reverse SEQ ID NO: 367 GTCTGCTGGATGAACTG (EX3) Forward SEQ ID NO: 368 CAG CAG AGC GAG CCT TGC AG Reverse SEQ ID NO: 369 CTG AGT GCC AGG AGG GC (Ex3) Forward SEQ ID NO: 370 CAC GGC CTG ACA GGG GCC (Ex3) Reverse SEQ ID NO: 371 GCC TAG GCT GGG CAC (EX4) Forward SEQ ID NO: 372 CTCTGAGTCCCATGCTGG (EX4) Reverse SEQ ID NO: 373 GACACCACTCTGGGGC (EX5) Forward SEQ ID NO: 374 TGCCCAGCCTAGGCCC (EX4) Reverse SEQ ID NO: 375 GCCAGAGGACACCACTC (EX5)

[0620] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0621] Probes for detecting RASSF7 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include:

TABLE-US-00074 SEQ ID NO: 376 GAGAGGTCCTTCACTGTGTGTACACAGCAAGAGCATGTGTGTGCCACTTC SEQ ID NO: 377 AGTGTCCTCCGAGCCAGGACAGGCATGTTGTTGGGACTGGCGGCCATGG AG SEQ ID NO: 378 GAGCCGGGCCCTGGAGGCAGCAGAGCGAGCCTTGCAGGCTCAGGCTCAG GAGCTG SEQ ID NO: 379 CGGCCTGACAGGGGCCCTCCTGGCACTCAGGGCCCTCTGCCTCCAGCCAG AGAGGAG SEQ ID NO: 380 GAGGAGCTGGGCCATGAGGCCTTCTGGGAGCAAGAGCTGCGCCGGGAGC AGGCCCGGGAG

[0622] Other probes to RASSF7 are known in the art and/or can be readily designed by the skilled artisan.

[0623] Antibodies against RASSF7 include, but are not limited to, LifeSpan BioSciences. Cat# LS-C31793-100 which is a rabbit polyclonal antibody; and from Novus Biologivals Cat#NB100-93434, which is a goat polyclonal anti-RASSF7 against the epitope SEQ ID NO:381 CTDLRGLELRVQRN.

Example 20

RNF183

[0624] RNF183 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that RNF183 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue as described in Example 2. It was surprisingly found that RNF183 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that RNF183 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0625] The sequence of an mRNA corresponding to RNF183 is given in ENSEMBL accession no. ENST00000297894 and has a sequence as in SEQ ID NO:382

TABLE-US-00075 CGATTCAGGGGAGGGAGCAACTGGAGCCTCAGGCCCTCCAGAGTAGTCTG CCTGACCACCCTGGAGCCCACAGAAGCCCAGGACGTCTCCCGCGAAGCCT CCCCGTGTGTGGCTGAGGATGGCTGAGCAGCAGGGCCGGGAGCTTGAGGC TGAGTGCCCCGTCTGCTGGAACCCCTTCAACAACACGTTCCATACCCCCA AAATGCTGGATTGCTGCCACTCCTTCTGCGTGGAATGTCTGGCCCACCTC AGCCTTGTGACTCCAGCCCGGCGCCGCCTGCTGTGCCCACTCTGTCGCCA GCCCACAGTGCTGGCCTCAGGGCAGCCTGTCACTGACTTGCCCACGGACA CTGCCATGCTCGCCCTGCTCCGCCTGGAGCCCCACCATGTCATCCTGGAA GGCCATCAGCTGTGCCTCAAGGACCAGCCCAAGAGCCGCTACTTCCTGCG CCAGCCTCAAGTCTACACGCTGGACCTTGGCCCCCAGCCTGGGGGCCAGA CTGGGCCGCCCCCAGACACGGCCTCTGCCACCGTGTCTACGCCCATCCTC ATCCCCAGCCACCACTCTTTGAGGGAGTGTTTCCGCAACCCTCAGTTCCG CATCTTTGCCTACCTGATGGCCGTCATCCTCAGTGTCACTCTGTTGCTCA TATTCTCCATCTTTTGGACCAAGCAGTTCCTTTGGGGTGTGGGGTGAGTG CTGTTCCCAGACAAGAAACCAAACCTTTTTCGGTTGCTGCTGGGTATGGT GACTACGGAGCCTCATTTGGTATTGTCTTCCTTTGTAGTGTTGTTTATTT TACAATCCAGGGATTGTTCAGGCCATGTGTTTGCTTCTGGGAACAATTTT AAAAAAAAACAAAAAAACGAAAAGCTTGAAGGACTGGGAGATGTGGAGCG ACCTCCGGGTGTGAGTGTGGCGTCATGGAAGGGCAGAGAAGCGGTTCTGA CCACAGAGCTCCACAGCAAGTTGTGCCAAAGGGCTGCACAGTGGTATCCA GGAACCTGACTAGCCCAAATAGCAAGTTGCATTTCTCACTGGAGCTGCTT CAAAATCAGTGCATATTTTTTTGAGTTGCTCTTTTACTATGGGTTGCTAA AAAAAAAAAAAAAATTGGGAAGTGAGCTTCAATTCTGTGGGTAAATGTGT GTTTGTTTCTCTTTGAATGTCTTGCCACTGGTTGCAGTAAAAGTGTTCTG TATTCATTAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

[0626] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000297894 and has a sequence as in SEQ ID NO:383

TABLE-US-00076 MAEQQGRELEAECPVCWNPFNNTFHTPKMLDCCHSFCVECLAHLSLVTPA RRRLLCPLCRQPTVLASGQPVTDLPTDTAMLALLRLEPHHVILEGHQLCL KDQPKSRYFLRQPQVYTLDLGPQPGGQTGPPPDTASATVSTPILIPSHHS LRECFRNPQFRIFAYLMAVILSVTLLLIFSIFWTKQFLWGVG

[0627] Primers for amplifying the sequence RNF183 can be designed using primer design software such as Oligo Calc.

[0628] Examples of primer pairs for amplifying RNF183 include those in

TABLE-US-00077 Forward SEQ ID NO: 384 GAGAAGCTGGGCTGGAG (EXON3) Reverse SEQ ID NO: 385 CAGCCACACACGGGGA (EXON4) Forward SEQ ID NO: 386 CAGCTGTGTGCTAAGAACAAAG (EXON3) Reverse SEQ ID NO: 387 GCCCTGCTGCTCAGCCATC (EXON4) Forward SEQ ID NO: 388 GCAGAAGGCAGCGAGGAC (EXON3) Reverse SEQ ID NO: 389 GGCAGCAATCCAGCATTTTG (EXON4) Forward SEQ ID NO: 390 CTGCGTGGAATGTCTGGCC (EXON4) Reverse SEQ ID NO: 391 CAAGTCAGTGACAGGCTGC (EXON4) Forward SEQ ID NO: 392 GTCTACACGCTGGACCTTG (EXON4) Reverse SEQ ID NO: 393 GATGCGGAACTGAGGGTTG (EXON4) Forward SEQ ID NO: 394 CTACCTGATGGCCGTCATC (EXON4) Reverse SEQ ID NO: 395 CCAGCAGCAACCGAAAAAG (EXON4) Forward SEQ ID NO: 396 CATGCGTGCAGGGCTGCA (EXON1) Reverse SEQ ID NO: 397 GTGCTGCTCTCCCAGGG (EXON2) Forward SEQ ID NO: 398 CCG TGGAATCGATTCCCAG (EXON2) Reverse SEQ ID NO: 399 CTGTTTCTCATATGGGTCATTCG (EXON3)

[0629] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0630] Probes for detecting RNF183 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

TABLE-US-00078 SEQ ID NO: 400 ATGGCTGAGCAGCAGGGCCGGGAGCTTGAGGCTGAGTGCCC SEQ ID NO: 401 GCCCACGGACACTGCCATGCTCGCCCTGCTCC SEQ ID NO: 402 GGACCAGCCCAAGAGCCGCTACTTCCTGCGCCAGCCT SEQ ID NO: 403 CGCTGGACCTTGGCCCCCAGCCTGGGGGCCAG SEQ ID NO: 404 GTTCCTTTGGGGTGTGGGGTGAGTGCTG

[0631] A probe for detecting RNF183 nucleic acid that was used on the microarray has a sequence as in

TABLE-US-00079 SEQ ID NO: 405 CAGTGGTATCCAGGAACCTGACTAGCCCAAATAGCAAGTTGCATTTCTCA CTGGAGCTGC

[0632] Other probes to RNF183 are known in the art and/or can be readily designed by the skilled artisan.

Example 21

SIRT6

[0633] SIRT6 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that SIRT6 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue as described in Example 2. It was surprisingly found that SIRT6 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that SIRT6 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0634] The sequence of an mRNA corresponding to SIRT6 is given in ENSEMBL accession no. ENST00000269860 and has a sequence as in SEQ ID NO:406

TABLE-US-00080 1 GCTTCCGGCGGAAGCGGCCTCAACAAGGGAAACTTTATTGTTCCCGTGGGGCAGTCGAGG 61 ATGTCGGTGAATTACGCGGCGGGGCTGTCGCCGTACGCGGACAAGGGCAAGTGCGGCCTC 121 CCGGAGATCTTCGACCCCCCGGAGGAGCTGGAGCGGAAGGTGTGGGAACTGGCGAGGCTG 181 GTCTGGCAGTCTTCCAGTGTGGTGTTCCACACGGGTGCCGGCATCAGCACTGCCTCTGGC 241 ATCCCCGACTTCAGGGACAAACTGGCAGAGCTCCACGGGAACATGTTTGTGGAAGAATGT 301 GCCAAGTGTAAGACGCAGTACGTCCGAGACACAGTCGTGGGCACCATGGGCCTGAAGGCC 361 ACGGGCCGGCTCTGCACCGTGGCTAAGGCAAGGGGGCTGCGAGCCTGCAGGGGAGAGCTG 421 AGGGACACCATCCTAGACTGGGAGGACTCCCTGCCCGACCGGGACCTGGCACTCGCCGAT 481 GAGGCCAGCAGATCCGGCCCAGCGGGAACCTGCCGCTGGCTACCAAGCGCCGGGGAGGCC 541 GCCTGGTCATCGTCAACCTGCAGCCCACCAAGCACGACCGCCATGCTGACCTCCGCATCC 601 ATGGCTACGTTGACGAGGTCATGACCCGGCTCATGAAGCACCTGGGGCTGGAGATCCCCG 661 CCTGGGACGGCCCCCGTGTGCTGGAGAGGGCGCTGCCACCCCTGCCCCGCCCGCCCACCC 721 CCAAGCTGGAGCCCAAGGAGGAATCTCCCACCCGGATCAACGGCTCTATCCCCGCCGGCC 781 CCAAGCAGGAGCCCTGCGCCCAGCACAACGGCTCAGAGCCCGCCAGCCCCAAACGGGAGC 841 GGCCCACCAGCCCTGCCCCCCACAGACCCCCCAAAAGGGTGAAGGCCAAGGCGGTCCCCA 901 GCTGACCAGGGTGCTTGGGGAGGGTGGGGCTTTTTGTAGAAACTGTGGATTCTTTTTCTC 961 TCGTGGTCTCACTTTGTTACTTGTTTCTGTCCCCGGGAGCCTCAGGGCTCTGAGAGCTGT 1021 GCTCCAGGCCAGGGGTTACACCTGCCCTCCGTGGTCCCTCCCTGGGCTCCAGGGGCCTCT 1081 GGTGCGGTTCCGGGAAGAAGCCACACCCCAGAGGTGACAGGTGAGCCCCTGCCACACCCC 1141 AGCCTCTGACTTGCTGTGTTGTCCAGAGGTGAGGCTGGGCCCTCCCTGGTCTCCAGCTTA 1201 AACAGGAGTGAACTCCCTCTGTCCCCAGGGCCTCCCTTCTGGGCCCCCTACAGCCCACCC 1261 TACCCCTCCTCCATGGGCCCTGCAGGAGGGGAGACCCACCTTGAAGTGGGGGATCAGTAG 1321 AGGCTTGCACTGCCTTTGGGGCTGGAGGGAGACGTGGGTCCACCAGGCTTCTGGAAAAGT 1381 CCTCAATGCAATAAAAACAATTTCTTTCTTGCA

[0635] The start and stop codons are indicated in bold as well as the position corresponding to the microarray probe.

[0636] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000269860 and has a sequence as in SEQ ID NO:407

TABLE-US-00081 1 MSVNYAAGLSPYADKGKCGLPEIFDPPEELERKVWELARLVWQSSSVVFHTGAGISTASG 61 IPDFRDKLAELHGNMFVEECAKCKTQYVRDTVVGTMGLKATGRLCTVAKARGLRACRGEL 121 RDTILDWEDSLPDRDLALADEASRSGPAGTCRWLPSAGEAAWSSSTCSPPSTTAMLTSAS 181 MATLTRS

[0637] Primers for amplifying the sequence SIRT6 can be designed using primer design software such as Oligo Calc and/or Primer 3.

[0638] Examples of primer pairs for amplifying SIRT6 include those in

TABLE-US-00082 Forward SEQ ID NO: 408 TTGTGGAAGAATGTGCCAAG Reverse SEQ ID NO: 409 CCTTAGCCACGGTGCAGAG Forward SEQ ID NO: 410 TCTTCCAGTGTGGTGTTCCA Reverse SEQ ID NO: 411 TTGGCACATTCTTCCACAAA Forward SEQ ID NO: 412 AGCTGAGGGACACCATCCTA Reverse SEQ ID NO: 413 GCAGGTTGACGATGACCAG Forward SEQ ID NO: 414 GCTTCCTGGTCAGCCAGA Reverse SEQ ID NO: 415 ATGTACCCAGCGTGATGGAC Forward SEQ ID NO: 416 GCTTCCTGGTCAGCCAGA Reverse SEQ ID NO: 417 CTAGGATGGTGTCCCTCAGC Forward SEQ ID NO: 418 GAGAGCTGAGGGACACCATC Reverse SEQ ID NO: 419 GTACCCAGCGTGATGGACAG Forward SEQ ID NO: 420 AGGATGTCGGTGAATTACGC Reverse SEQ ID NO: 421 AAAGGTGGTGTCGAACTTGG

[0639] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0640] Probes for detecting SIRT6 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

TABLE-US-00083 SEQ ID NO: 422 TGTAAGACGCAGTACGTCCG SEQ ID NO: 423 GACTTCAGGGACAAACTGGC SEQ ID NO: 424 ACTGGGAGGACTCCCTGC SEQ ID NO: 425 TGTAAGACGCAGTACGTCCG SEQ ID NO: 426 TGTAAGACGCAGTACGTCCG SEQ ID NO: 427 TAGACTGGGAGGACTCCCTG SEQ ID NO: 428 GAGTCTGGACCATGGAGGAG

[0641] A probe to detect SIRT6 nucleic acid that was used on the microarray has a sequence as in

TABLE-US-00084 SEQ ID NO: 429 GAAGTGGGGGATCAGTAGAGGCTTGCACTGCCTTTGGGGCTGGAGGGAGA

[0642] Other probes to SIRT6 are known in the art and/or can be readily designed by the skilled artisan.

[0643] Antibodies against SIRT6 include, but are not limited to, Rabbit polyclonal anti-SIRT6 against de C-terminal Cat#2590 from Cell Signalling Technology; and Mouse monoclonal antibody raised against a partial recombinant SIRT6 141 a.a. .about.251 a.a Catalog #:H00051548-M01 from abnova.

Example 22

TJP3

[0644] TJP3, tight junction protein 3 (zona occludens 3) also known as MGC119546, ZO-3, ZO3 was found to be overexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that TJP3 was overexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue as described in Example 2. It was surprisingly found that TJP3 was overexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that TJP3 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0645] TJP3 (ZO-3) was first identified as a 130 kDa protein that coimmunoprecipitates with ZO-1. It is a member of the MAGUK proteins (MEMBRANE-associated guanylate kinase-like homologues). These proteins are implicated in the formation and maintenance of supramolecular complexes at specific areas of the cell surface called tight junctions. Tight junctions locate at the most apical part of lateral membranes of simple epithelial cells, and are considered to be involved in barrier and fence functions.

[0646] Cloning and sequencing cDNAs encoding MAGUK proteins showed that all have three PDZ domains (PDZ1 to -3), one SH3 domain, and one guanylate kinase-like (GUK) domain in this order from their NH2 termini (PMID: 10966866). Among these domains, PDZ domains bind to COOH-terminal ends of various proteins, especially integral membrane proteins, most of which end in valine. Thus, MAGUKs can cross-link multiple integral membrane proteins at the cytoplasmic surface of plasma membranes to establish specialized membrane domains. ZO-3 has also been reported to associate with ZO-1, but not with ZO-2, although the domains responsible for ZO-3/ZO-1 interaction remain unidentified. ZO-3 was also shown to directly bind to the cytoplasmic domain of occluding (Haskins et al. 1998).

[0647] The sequence of an mRNA corresponding to TJP3 is given in ENSEMBL accession no. ENST00000262968 and has a sequence as in SEQ ID NO:430

TABLE-US-00085 ATGAACCTGTGTGGCCTCATGCCCATCTTCCCCGCTCCCCTCGACCAGGT GGCTGACATGGAGGAGCTGACCATCTGGGAACAGCACACGGCCACACTGT CCAAGGACCCCCGCCGGGGCTTTGGCATTGCGATCTCTGGAGGCCGAGAC CGGCCCGGTGGATCCATGGTTGTATCTGACGTGGTACCTGGAGGGCCGGC GGAGGGCAGGCTACAGACAGGCGACCACATCGTCATGGTGAACGGGGTTT CCATGGAGAATGCCACCTCCGCGTTTGCCATTCAGATACTCAAGACCTGC ACCAAGATGGCCAACATCACAGTGAAACGTCCCCGGAGGATCCACCTGCC CGCCACCAAAGCCAGCCCCTCCAGCCCAGGGCGCCAGGACTCGGATGAAG ACGATGGGCCCCAGCGGGTGGAGGAGGTGGACCAGGGCCGGGGCTATGAC GGCGACTCATCCAGTGGCTCCGGCCGCTCCTGGGACGAGCGCTCCCGCCG GCCGAGGCCTGGTCGCCGGGGCCGGGCCGGCAGCCATGGGCGTAGGAGCC CAGGTGGTGGCTCTGAGGCCAACGGGCTGGCCCTGGTGTCCGGCTTTAAG CGGCTGCCACGGCAGGACGTGCAGATGAAGCCTGTGAAGTCAGTGCTGGT GAAGAGGAGAGACAGCGAAGAGTTTGGCGTCAAGCTGGGCAGTCAGATCT TCATCAAGCACATTACAGATTCGGGCCTGGCTGCCCGGCACCGTGGGCTG CAGGAAGGAGATCTCATTCTACAGATCAACGGGGTGTCTAGCCAGAACCT GTCACTGAACGACACCCGGCGACTGATTGAGAAGTCAGAAGGGAAGCTAA GCCTGCTGGTGCTGAGAGATCGTGGGCAGTTCCTGGTGAACATTCCGCCT GCTGTCAGTGACAGCGACAGCTCGCCATTGGAGGAAGGCGTGACCATGGC TGATGAGATGTCCTCTCCCCCTGCAGACATCTCGGACCTCGCCTCGGAGC TATCGCAGGCACCACCATCCCACATCCCACCACCACCCCGGCATGCTCAG CGGAGCCCCGAGGCCAGCCAGACCGACTCTCCCGTGGAGAGTCCCCGGCT TCGGCGGGAAAGTTCAGTAGATTCCAGAACCATCTCGGAACCAGATGAGC AACGGTCAGAGTTGCCCAGGGAAAGCAGCTATGACATCTACAGAGTGCCC AGCAGTCAGAGCATGGAGGATCGTGGGTACAGCCCCGACACGCGTGTGGT CCGCTTCCTCAAGGGCAAGAGCATCGGGCTGCGGCTGGCAGGGGGCAATG ACGTGGGCATCTTCGTGTCCGGGGTGCAGGCGGGCAGCCCGGCCGACGGG CAGGGCATCCAGGAGGGAGATCAGATTCTGCAGGTGAATGACGTGCCATT CCAGAACCTGACACGGGAGGAGGCAGTGCAGTTCCTGCTGGGGCTGCCAC CAGGCGAGGAGATGGAGCTGGTGACGCAGAGGAAGCAGGACATTTTCTGG AAAATGGTGCAGTCCCGCGTGGGTGACTCCTTCTACATCCGCACTCACTT TGAGCTGGAGCCCAGTCCACCGTCTGGCCTGGGCTTCACCCGTGGCGACG TCTTCCACGTGCTGGACACGCTGCACCCCGGCCCCGGGCAGAGCCACGCA CGAGGAGGCCACTGGCTGGCGGTGCGCATGGGTCGTGACCTGCGGGAGCA AGAGCGGGGCATCATTCCCAACCAGAGCAGGGCGGAGCAGCTGGCCAGCC TGGAAGCTGCCCAGAGGGCCGTGGGAGTCGGGCCCGGCTCCTCCGCGGGC TCCAATGCTCGGGCCGAGTTCTGGCGGCTGCGGGGTCTTCGTCGAGGAGC CAAGAAGACCACTCAGCGGAGCCGTGAGGACCTCTCAGCTCTGACCCGAC AGGGCCGCTACCCGCCCTACGAACGAGTGGTGTTGCGAGAAGCCAGTTTC AAGCGCCCGGTAGTGATCCTGGGACCCGTGGCCGACATTGCTATGCAGAA GTTGACTGCTGAGATGCCTGACCAGTTTGAAATCGCAGAGACTGTGTCCA GGACCGACAGCCCCTCCAAGATCATCAAACTAGACACCGTGCGGGTGATT GCAGAAAAAGACAAGCATGCGCTCCTGGATGTGACCCCCTCCGCCATCGA GCGCCTCAACTATGTGCAGTACTACCCCATTGTGGTCTTCTTCATCCCCG AGAGCCGGCCGGCCCTCAAGGCACTGCGCCAGTGGCTGGCGCCTGCCTCC CGCCGCAGCACCCGTCGCCTCTACGCACAAGCCCAGAAGCTGCGAAAACA CAGCAGCCACCTCTTCACAGCCACCATCCCTCTGAATGGCACGAGTGACA CCTGGTACCAGGAGCTCAAGGCCATCATTCGAGAGCAGCAGACGCGGCCC ATCTGGACGGCGGAAGATCAGCTGGATGGCTCCTTGGAGGACAACCTAGA CCTCCCTCACCACGGCCTGGCCGACAGCTCCGCTGACCTCAGCTGCGACA GCCGCGTTAACAGCGACTACGAGACGGACGGCGAGGGCGGCGCGTACACG GATGGCGAGGGCTACACAGACGGCGAGGGGGGGCCCTACACGGATGTGGA TGATGAGCCCCCGGCTCCAGCCCTGGCCCGGTCCTCGGAGCCCGTGCAGG CAGATGAGTCCCAGAGCCCGAGGGATCGTGGGAGAATCTCGGCTCATCAG GGGGCCCAGGTGGACAGCCGCCACCCCCAGGGACAGTGGCGACAGGACAG CATGCGAACCTATGAACGGGAAGCCCTGAAGAAAAAGTTTATGCGAGTAC ATGATGCGGAGTCCTCCGATGAAGACGGCTATGACTGGGGTCCGGCCACT GACCTGTGA

[0648] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000262968 and has a sequence as in SEQ ID NO:431

TABLE-US-00086 MNLCGLMPIFPAPLDQVADMEELTIWEQHTATLSKDPRRGFGIAISGGRD RPGGSMVVSDVVPGGPAEGRLQTGDHIVMVNGVSMENATSAFAIQILKTC TKMANITVKRPRRIHLPATKASPSSPGRQDSDEDDGPQRVEEVDQGRGYD GDSSSGSGRSWDERSRRPRPGRRGRAGSHGRRSPGGGSEANGLALVSGFK RLPRQDVQMKPVKSVLVKRRDSEEFGVKLGSQIFIKHITDSGLAARHRGL QEGDLILQINGVSSQNLSLNDTRRLIEKSEGKLSLLVLRDRGQFLVNIPP AVSDSDSSPLEEGVTMADEMSSPPADISDLASELSQAPPSHIPPPPRHAQ RSPEASQTDSPVESPRLRRESSVDSRTISEPDEQRSELPRESSYDIYRVP SSQSMEDRGYSPDTRVVRFLKGKSIGLRLAGGNDVGIFVSGVQAGSPADG QGIQEGDQILQVNDVPFQNLTREEAVQFLLGLPPGEEMELVTQRKQDIFW KMVQSRVGDSFYIRTHFELEPSPPSGLGFTRGDVFHVLDTLHPGPGQSHA RGGHWLAVRMGRDLREQERGIIPNQSRAEQLASLEAAQRAVGVGPGSSAG SNARAEFWRLRGLRRGAKKTTQRSREDLSALTRQGRYPPYERVVLREASF KRPVVILGPVADIAMQKLTAEMPDQFEIAETVSRTDSPSKIIKLDTVRVI AEKDKHALLDVTPSAIERLNYVQYYPIVVFFIPESRPALKALRQWLAPAS RRSTRRLYAQAQKLRKHSSHLFTATIPLNGTSDTWYQELKAIIREQQTRP IWTAEDQLDGSLEDNLDLPHHGLADSSADLSCDSRVNSDYETDGEGGAYT DGEGYTDGEGGPYTDVDDEPPAPALARSSEPVQADESQSPRDRGRISAHQ GAQVDSRHPQGQWRQDSMRTYEREALKKKFMRVHDAESSDEDGYDWGPAT DL

[0649] Primers for amplifying the sequence ENST00000262968 can be designed using primer design software such as Oligo Calc and/or Primer 3.

[0650] Examples of primer pairs for amplifying TJP3 include:

TABLE-US-00087 Forward SEQ ID NO: 432 CCCTCGACCAGGTGGCTGAC (Exon1) Reverse SEQ ID NO: 433 CCTCCAGAGATCGCAATGC (Exon2) Forward SEQ ID NO: 434 GTATCTGACGTGGTACCTG (Exon2) Reverse SEQ ID NO: 435 GGCAAACGCGGAGGTGGCATTC (Exon3) Forward SEQ ID NO: 436 CGGGGTTTCCATGGAGAATG (Exon3) Reverse SEQ ID NO: 437 GCGGGCAGGTGGATCCTCC (Exon4) Forward SEQ ID NO: 438 GCAGGACGTGCAGATGAAGC (Exon4) Reverse SEQ ID NO: 439 CCCGAATCTGTAATGTGCTTG (Exon5) Forward SEQ ID NO: 440 GTGGGCTGCAGGAAGGAGATC (Exon5) Reverse SEQ ID NO: 441 GAACTGCCCACGATCTCTCAGC (Exon6) Forward SEQ ID NO: 442 GATCGTGGGCAGTTCCTGG (Exon6) Reverse SEQ ID NO: 443 GATGTCTGCAGGGGGAGAGG (Exon7) Forward SEQ ID NO: 444 CACCCCGGCATGCTCAGCG (Exon7) Reverse SEQ ID NO: 445 CCGAGATGGTTCTGGAATC (Exon8) Forward SEQ ID NO: 446 GAGTCCCCGGCTTCGGCGG (Exon8) Reverse SEQ ID NO: 447 CGATCCTCCATGCTCTGACTG (Exon9) Forward SEQ ID NO: 448 GTG CAG GCG GGC AGC CCG (Exon10) Reverse SEQ ID NO: 449 GTC CTG CTT CCT CTG CGT C (Exon11) Forward SEQ ID NO: 450 CGAGAGCAGCAGACGCGGCC Reverse SEQ ID NO: 451 GAGGTCAGCGGAGCTGTCG

[0651] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0652] Probes for detecting TJP3 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents).

[0653] Other examples of probes include:

TABLE-US-00088 SEQ ID NO: 452 CAGGGACAGTGGCGACAGGACAGCATGCGAACCTATGAACGGGAAGCCCT GAAGAAAAAG SEQ ID NO: 453 GAACAGCACACGGCCACACTGTCCAAGGACCCCCGCCGGGGC SEQ ID NO: 454 ACCAAGATGGCCAACATCACAGTGAAACGTCCCCGGAGGATCCACCTGCC CGCC SEQ ID NO: 455 CAGTGACAGCGACAGCTCGCCATTGGAGGAAGGCGTGACCATGGCTGATG AGAT SEQ ID NO: 456 CGAGTGGTGTTGCGAGAAGCCAGTTTCAAGCGCCCGGTAGTGATCCTGGG ACCC

[0654] Other probes to TJP3 are known in the art and/or can be readily designed by the skilled artisan.

[0655] Antibodies against include, but are not limited to, TJP3 are commercially available from e.g., Abnova Cat# H00027134-A01 which is a mouse polyclonal antibody raised against a partial recombinant TJP3 having the sequence SEQ ID NO:457 DEPPAPALARSSEPVQADESQSPRDRGRISAHQGAQVDSRHPQGQWRQDS MRTYEREALKKKFMRVHDAESSDEDGYDWGPATDL (NP.sub.--055243, 868 a.a. .about.953 a.a); from LifeSpanBiosciences Cat# LS-C18593 which is a rabbit polyclonal against a synthetic peptide derived from the C-terminus of the human TJP3 (ZO-3) protein; and from LifeSpanBiosciences Cat#LS-050518 which is a rabbit polyclonal against a synthetic peptide derived from the C-terminus of the human TJP3 (ZO-3) protein.

Example 23

EFEMP2

[0656] EFEMP2 also known as FBLN4, MBP1, and UPH1 was found to be underexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that EFEMP2 was underexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue as described in Example 2. It was surprisingly found that EFEMP2 was underexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that EFEMP2 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer. ENSG00000172638: Just one transcript

[0657] The sequence of an mRNA corresponding to EFEMP2 is given in ENSEMBL accession number ENST00000307998 and has a sequence as in SEQ ID NO:458.

TABLE-US-00089 GGGGCGCTTCCTGGGGCCGCGCGTCCAGGGAGCTGTGCCGTCCGCCCGTC CGTCTGCCCGCAGGCATTGCCCGAGCCAGCCGAGCCGCCAGAGCCGCGGG CCGCGGGGGTGTCGCGGGCCCAACCCCAGGATGCTCCCCTGCGCCTCCTG CCTACCCGGGTCTCTACTGCTCTGGGCGCTGCTACTGTTGCTCTTGGGAT CAGCTTCTCCTCAGGATTCTGAAGAGCCCGACAGCTACACGGAATGCACA GATGGCTATGAGTGGGACCCAGACAGCCAGCACTGCCGGGATGTCAACGA GTGTCTGACCATCCCTGAGGCCTGCAAGGGGGAAATGAAGTGCATCAACC ACTACGGGGGCTACTTGTGCCTGCCCCGCTCCGCTGCCGTCATCAACGAC CTACACGGCGAGGGACCCCCGCCACCAGTGCCTCCCGCTCAACACCCCAA CCCCTGCCCACCAGGCTATGAGCCCGACGATCAGGACAGCTGTGTGGATG TGGACGAGTGTGCCCAGGCCCTGCACGACTGTCGCCCCAGCCAGGACTGC CATAACTTGCCTGGCTCCTATCAGTGCACCTGCCCTGATGGTTACCGCAA GATCGGGCCCGAGTGTGTGGACATAGACGAGTGCCGCTACCGCTACTGCC AGCACCGCTGCGTGAACCTGCCTGGCTCCTTCCGCTGCCAGTGCGAGCCG GGCTTCCAGCTGGGGCCTAACAACCGCTCCTGTGTTGATGTGAACGAGTG TGACATGGGGGCCCCATGCGAGCAGCGCTGCTTCAACTCCTATGGGACCT TCCTGTGTCGCTGCCACCAGGGCTATGAGCTGCATCGGGATGGCTTCTCC TGCAGTGATATTGATGAGTGTAGCTACTCCAGCTACCTCTGTCAGTACCG CTGCGTCAACGAGCCAGGCCGTTTCTCCTGCCACTGCCCACAGGGTTACC AGCTGCTGGCCACACGCCTCTGCCAAGACATTGATGAGTGTGAGTCTGGT GCGCACCAGTGCTCCGAGGCCCAAACCTGTGTCAACTTCCATGGGGGCTA CCGCTGCGTGGACACCAACCGCTGCGTGGAGCCCTACATCCAGGTCTCTG AGAACCGCTGTCTCTGCCCGGCCTCCAACCCTCTATGTCGAGAGCAGCCT TCATCCATTGTGCACCGCTACATGACCATCACCTCGGAGCGGAGCGTGCC CGCTGACGTGTTCCAGATCCAGGCGACCTCCGTCTACCCCGGTGCCTACA ATGCCTTTCAGATCCGTGCTGGAAACTCGCAGGGGGACTTTTACATTAGG CAAATCAACAACGTCAGCGCCATGCTGGTCCTCGCCCGGCCGGTGACGGG CCCCCGGGAGTACGTGCTGGACCTGGAGATGGTCACCATGAATTCCCTCA TGAGCTACCGGGCCAGCTCTGTACTGAGGCTCACCGTCTTTGTAGGGGCC TACACCTTCTGAGGAGCAGGAGGGAGCCACCCTCCCTGCAGCTACCCTAG CTGAGGAGCCTGTTGTGAGGGGCAGAATGAGAAAGGCAATAAAGGGAGAA AGAAAGTCCTGGTGGCTGAGGTGGGCGGGTCACACTGCAGGAAGCCTCAG GCTGGGGCAGGGTGGCACTTGGGGGGGCAGGCCAAGTTCACCTAAATGGG GGTCTCTATATGTTCAGGCCCAGGGGCCCCCATTGACAGGAGCTGGGAGC TCTGCACCACGAGCTTCAGTCACCCCGAGAGGAGAGGAGGTAACGAGGAG GGCGGACTCCAGGCCCCGGCCCAGAGATTTGGACTTGGCTGGCTTGCAGG GGTCCTAAGAAACTCCACTCTGGACAGCGCCAGGAGGCCCTGGGTTCCAT TCCTAACTCTGCCTCAAACTGTACATTTGGATAAGCCCTAGTAGTTCCCT GGGCCTGTTTTTCTATAAAACGAGGCAACTGGACTGTT

[0658] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000309953 and has a sequence as in SEQ ID NO:459

TABLE-US-00090 MLPCASCLPGSLLLWALLLLLLGSASPQDSEEPDSYTECTDGYEWDPDSQ HCRDVNECLTIPEACKGEMKCINHYGGYLCLPRSAAVINDLHGEGPPPPV PPAQHPNPCPPGYEPDDQDSCVDVDECAQALHDCRPSQDCHNLPGSYQCT CPDGYRKIGPECVDIDECRYRYCQHRCVNLPGSFRCQCEPGFQLGPNNRS CVDVNECDMGAPCEQRCFNSYGTFLCRCHQGYELHRDGFSCSDIDECSYS SYLCQYRCVNEPGRFSCHCPQGYQLLATRLCQDIDECESGAHQCSEAQTC VNFEIGGYRCVDTNRCVEPYIQVSENRCLCPASNPLCREQPSSIVHRYMT ITSERSVPADVFQIQATSVYPGAYNAFQIRAGNSQGDFYIRQINNVSAML VLARPVTGPREYVLDLEMVTMNSLMSYRASSVLRLTVFVGAYTF

[0659] Examples of primer pairs for amplifying EFEMP2 include those in

TABLE-US-00091 Forward SEQ ID NO: 460 TGCTCTTGGGATCAGCTTCT Reverse SEQ ID NO: 461 CCTCAGGGATGGTCAGACAC Forward SEQ ID NO: 462 TGCCCACCAGGCTATGAG Reverse SEQ ID NO: 463 CAGGCAAGTTATGGCAGTCC Forward SEQ ID NO: 464 AACTTGCCTGGCTCCTATCA Reverse SEQ ID NO: 465 GTGCTGGCAGTAGCGGTAG Forward SEQ ID NO: 466 GGCCTAACAACCGCTCCT Reverse SEQ ID NO: 467 CGACACAGGAAGGTCCCATA Forward SEQ ID NO: 468 TATGGGACCTTCCTGTGTCG Reverse SEQ ID NO: 469 GATGCAGCGGTACTGACAGA Forward SEQ ID NO: 470 GTCAGTACCGCTGCATCAAC Reverse SEQ ID NO: 471 CGCACCAGACTCACACTCAT Forward SEQ ID NO: 472 GTGGAGCCCTACATCCAGGT Reverse SEQ ID NO: 473 TCCGAGGTGATGGTCATGTA

[0660] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0661] Probes for detecting EFEMP2 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

[0662] The probe used on the microarray has a sequence as in

TABLE-US-00092 SEQ ID NO: 474 TTCATCCATTGTGCACCGCTACATGACCATCACCTCGGAGCGGAGCGTGC SEQ ID NO: 475 GAAGAGCCCGACAGCTACAC SEQ ID NO: 476 CAGGCAAGTTATGGCAGTCC SEQ ID NO: 477 CCTGATGGTTACCGCAAGAT SEQ ID NO: 478 GTGAACGAGTGTGACATGGG SEQ ID NO: 479 ATGGCTTCTCCTGCAGTGAT SEQ ID NO: 480 ACGCCTCTGCCAAGACATT SEQ ID NO: 481 ATGTCGAGAGCAGCCTTCAT

[0663] Antibodies to EFEMP2 include Mouse Anti-Human EFEMP2 MaxPab.RTM. Polyclonal Antibody, Unconjugated Cat# H00030008-B01 against full length human EFEMP2; Anti-EFEMP2 Monoclonal Antibody, Unconjugated, Clone 2C8 Cat# H00030008-M01 against a partial protein, 26aa-443aa; and Rabbit Anti-Human EFEMP2 Polyclonal Antibody, Unconjugated Cat# ab74873 against a Synthetic peptide derived from an internal region of human EFEMP2.

Example 24

SOCS2

[0664] SOCS2 also known as CIS2, Cish2, SOCS-2, SSI-2, SSI2, and STATI2 was found to be underexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that SOCS2 was underexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue as described in Example 2. It was surprisingly found that SOCS2 was underexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that SOCS2 can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0665] The sequence of an mRNA corresponding to SOCS2 is given in ENSEMBL accession number ENST00000340600 and has a sequence as in SEQ ID NO:482

TABLE-US-00093 1 AGCCGCGGCCTCAACTAAAAGTGGCCATTGACCTTTCAAGCTTTCGAGCAGTGATGCAAT 61 AGAATAGTATTTCAAAGAAAAATGCTTATCGAAATTTTGGATCCGGTTTTCCCGTGATTG 121 TTAAGGGTTTCTTTTAAAAAGTAGGTCACATTTCAAGTAGGTCATATTTCGGGGGCGGGT 181 GCGCAGACAAGGAGATGAGTTTCCACTAAGGCCAGGGGGCCTCCAACGGGGTTGGAGGTG 241 AGAATCCCAGGTAGGGTAGAGGTGCCGAGATCCTTCCGAATCCCAGCCCTGGGGCGTCAG 301 CCCTGCAGGGAATGGCAGAGACACTCTCCGGACTGAGGGAACCGAGGCCAGTCACCAAGC 361 CCCTTCCGGGCGCGCAGGCGATCAGTGGGTGACCGCGGCTGCGAGGGACTTTGTCATCCG 421 TCCTCCAGGATCTGGGGAGAAAGAGCCCCATCCCTTCTCTCTCTGCCACCATTTCGGACA 481 CCCCGCAGGGACTCGTTTTGGGATTCGCACTGACTTCAAGGAAGGACGCGAACCCTTCTC 541 TGACCCCAGCTCGGGCGGCCACCTGTCTTTGCCGCGGTGACCCTTCTCTCATGACCCTGC 601 GGTGCCTTGAGCCCTCCGGGAATGGCGGGGAAGGGACGCGGAGCCAGTGGGGGACCGCGG 661 GGTCGGCGGAGGAGCCATCCCCGCAGGCGGCGCGTCTGGCGAAGGCCCTGCGGGAGCTCG 721 GTCAGACAGGATGGTACTGGGGAAGTATGACTGTTAATGAAGCCAAAGAGAAATTAAAAG 781 AGGCACCAGAAGGAACTTTCTTGATTAGAGATAGCTCGCATTCAGACTACCTACTAACAA 841 TATCTGTTAAAACATCAGCTGGACCAACTAATCTTCGAATCGAATACCAAGACGGAAAAT 901 TCAGATTGGACTCTATCATATGTGTCAAATCCAAGCTTAAACAATTTGACAGTGTGGTTC 961 ATCTGATCGACTACTATGTTCAGATGTGCAAGGATAAGCGGACAGGTCCAGAAGCCCCCC 1021 GGAACGGCACTGTTCACCTTTATCTGACCAAACCGCTCTACACGTCAGCACCATCTCTGC 1081 AGCATCTCTGTAGGCTCACCATTAACAAATGTACCGGTGCCATCTGGGGACTGCCTTTAC 1141 CAACAAGACTAAAAGATTACTTGGAAGAATATAAATTCCAGGTATAAATGTTTCTCTTTT 1201 TTTAAACATGTCTCACATAGAGTATCTCCGAATGCAGCTATGTAAAAGAGAACCAAAACT 1261 TGAGTGCTCTGGATAACTATATGGAATGCTTTCTAAGAACAGCTGAAGCTAATCTAATTT 1321 AAATTTAACAGCTTGAAGAGGTAGCTAGGTGTTTAAAGTTCCTCCAGATACTTTTACCTG 1381 AGTGATGCTTCCCTTCCTAAGGCTGACCAAGACCTGTTGATCCTTTTAGATTAAAAATAA 1441 AATGTCGCATGTAAAGGCTGAAGTCGCGTTTTATCAGAATGCCTTGCCTTCTTAGGTTCT 1501 TTTCCATTATGTCAAAGGTCCAGGCTCCAGTAGGAGAGAAAGAACTCCTCATAGGAATAC 1561 TGAAGAAGTGGGAAGGAACCAAGCTGACACAGGCCTCACTGCAATTTGATATGCCTGCTG 1621 ATCAGAGTCTCTTGGGCATTTTATATTTTGCATTCTGATGTACCTAGGAGTTTTGTTAAA 1681 CAGATGATGTATGTGAGTATTTATCCCATTTTATGCAATTAACCAAATCAACCAAAAAAA 1741 GTGACCATGAAGTCCTGTATTTGTCTTTTTACTACATGTAGGAACTCTCATGTGAATGAG 1801 TACTGTAGTAATCCATTCTATGGGAGCCTTATTTCAGAAATATTTCAAACTGGTGCAAAT 1861 GGAAAAGACTTTCTCTTTTCCTTTAAAGCTAAAGACAAGAATATCATGCTATACAGGTGC 1921 AACTCAATCCCCGTTAATAAAAACCAATGTAGGTATAGGCATTCTACCCTTTGAAATAGC 1981 TGTGTCCCAACCTGTTGCCATTGATTTTTTGGAAATGGCTTTAGAAATATCCAAGTTGTC 2041 CTTGAATTGTCTAACCATGGACATAAACAGTTGTCTCCCTTCTACTGTGTAGAATACTTT 2101 GACTTAATTTTCTTCCAGATACAGGGGGATACCTGCCTGTTTTTCAAAGTGTTTATTTAC 2161 TGCTGTTACTATTTGATTAGAATGTATTAAATAAAAAAAACCTGATTTCT

[0666] The start and stop codons are indicated in bold.

[0667] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000339428 and has a sequence as in SEQ ID NO:483

TABLE-US-00094 1 MTLRCLEPSGNGGEGTRSQWGTAGSAEEPSPQAARLAKALRELGQTGWYWGSMTVNEAKE 61 KLKEAPEGTFLIRDSSHSDYLLTISVKTSAGPTNLRIEYQDGKFRLDSIICVKSKLKQFD 121 SVVHLIDYYVQMCKDKRTGPEAPRNGTVHLYLTKPLYTSAPSLQHLCRLTINKCTGAIWG 181 LPLPTRLKDYLEEYKFQV

[0668] Examples of primer pairs for amplifying SOCS2 include those in

TABLE-US-00095 Forward SEQ ID NO: 484 AGTCACCAAGCCCCTTCC Reverse SEQ ID NO: 485 GCTCTTTCTCCCCAGATCCT Forward SEQ ID NO: 486 GGGACTGCCTTTACCAACAA Reverse SEQ ID NO: 487 TTTACATAGCTGCATTCGGAGA

[0669] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art (e.g., using Oligo Calc and/or Primer 3).

[0670] Probes for detecting SOCS2 can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

[0671] The probe used on the microarray has a sequence as in

TABLE-US-00096 SEQ ID NO: 488 AGTGTGGTTCATCTGATCGACTACTATGTTCAGATGTGCAAGGATAAGCG GACAGGTCCA SEQ ID NO: 489 GACTTTGTCATCCGTCCTCC SEQ ID NO: 490 ACTTGGAAGAATATAAATTCCAGGT

[0672] Antibodies to SOCS2 include, but are not limited to, Mouse Anti-Human SOCS2 Polyclonal Antibody, Unconjugated Cat# H00008835-A01 against a partial protein: 99aa-198aa; Mouse Anti-Human SOCS2 Monoclonal Antibody, Unconjugated, Clone 3E7 Cat# H00008835-M01 againts a partial protein: 99aa-198aa; Rabbit Anti-Human SOCS2 Polyclonal Antibody, Unconjugated Cat# ab74533 against the C-terminal part of the protein.

Example 25

DCN

[0673] DCN also known as CSCD, DSPG2, PG40, PGII, PGS2, and SLRR1B was found to be underexpressed in endometrial cancer primary tissue as compared to normal endometrial tissue by the microarray experiment described in Example 1. Further studies using RT-PCR demonstrated that DCN was underexpressed in primary endometrial cancer tissue as compared to normal endometrial tissue as described in Example 2. It was surprisingly found that DCN was underexpressed in samples obtained from uterine fluid (e.g., aspirates) from patients having endometrial cancer by the method described in Example 4. Example 5 shows that DCN can be combined with other biomarkers to give excellent predictive power for diagnosis of endometrial cancer.

[0674] Six transcripts from gene ENSG00000011465 but only 4 of them hybridize with our array probe, the following ones:

[0675] The sequence of an mRNA corresponding to DCN is given in ENSEMBL accession number ENST00000052754 and has a sequence as in SEQ ID NO:491

TABLE-US-00097 1 GAATCTACAATAAGACAAATTTCAAATCAAGTTGCTCCACTATACTGCATAAGCAGTTTA 61 GAATCTTAAGCAGATGCAAAAAGAATAAAGCAAATGGGAGGAAAAAAAAGGCCGATAAAG 121 TTTCTGGCTACAATACAAGAGACATATCATTACCATATGATCTAATGTGGGTGTCAGCCG 181 GATTGTGTTCATTGAGGGAAACCTTATTTTTTAACTGTGCTATGGAGTAGAAGCAGGAGG 241 TTTTCAACCTAGTCACAGAGCAGCACCTACCCCCTCCTCCTTTCCACACCTGCAAACTCT 301 TTTACTTGGGCTGAATATTTAGTGTAATTACATCTCAGCTTTGAGGGCTCCTGTGGCAAA 361 TTCCCGGATTAAAAGGTTCCCTGGTTGTGAAAATACATGAGATAAATCATGAAGGCCACT 421 ATCATCCTCCTTCTGCTTGCACAAGTTTCCTGGGCTGGACCGTTTCAACAGAGAGGCTTA 481 TTTGACTTTATGCTAGAAGATGAGGCTTCTGGGATAGGCCCAGAAGTTCCTGATGACCGC 541 GACTTCGAGCCCTCCCTAGGCCCAGTGTGCCCCTTCCGCTGTCAATGCCATCTTCGAGTG 601 GTCCAGTGTTCTGATTTGGGTCTGGACAAAGTGCCAAAGGATCTTCCCCCTGACACAACT 661 CTGCTAGACCTGCAAAACAACAAAATAACCGAAATCAAAGATGGAGACTTTAAGAACCTG 721 AAGAACCTTCACGCATTGATTCTTGTCAACAATAAAATTAGCAAAGTTAGTCCTGGAGCA 781 TTTACACCTTTGGTGAAGTTGGAACGACTTTATCTGTCCAAGAATCAGCTGAAGGAATTG 841 CCAGAAAAAATGCCCAAAACTCTTCAGGAGCTGCGTGCCCATGAGAATGAGATCACCAAA 901 GTGCGAAAAGTTACTTTCAATGGACTGAACCAGATGATTGTCATAGAACTGGGCACCAAT 961 CCGCTGAAGAGCTCAGGAATTGAAAATGGGGCTTTCCAGGGAATGAAGAAGCTCTCCTAC 1021 ATCCGCATTGCTGATACCAATATCACCAGCATTCCTCAAGGTCTTCCTCCTTCCCTTACG 1081 GAATTACATCTTGATGGCAACAAAATCAGCAGAGTTGATGCAGCTAGCCTGAAAGGACTG 1141 AATAATTTGGCTAAGTTGGGATTGAGTTTCAACAGCATCTCTGCTGTTGACAATGGCTCT 1201 CTGGCCAACACGCCTCATCTGAGGGAGCTTCACTTGGACAACAACAAGCTTACCAGAGTA 1261 CCTGGTGGGCTGGCAGAGCATAAGTACATCCAGGTTGTCTACCTTCATAACAACAATATC 1321 TCTGTAGTTGGATCAAGTGACTTCTGCCCACCTGGACACAACACCAAAAAGGCTTCTTAT 1381 TCGGGTGTGAGTCTTTTCAGCAACCCGGTCCAGTACTGGGAGATACAGCCATCCACCTTC 1441 AGATGTGTCTACGTGCGCTCTGCCATTCAACTCGGAAACTATAAGTAATTCTCAAGAAAG 1501 CCCTCATTTTTATAACCTGGCAAAATCTTGTTAATGTCATTGCTAAAAAATAAATAAAAG 1561 CTAGATACTGGAAACCTAACTGCAATGTGGATGTTTTACCCACATGACTTATTATGCATA 1621 AAGCCAAATTTCCAGTTTAAGTAATTGCCTACAATAAAAAGAAATTTTGCCTGCCATTTT 1681 CAGAATCATCTTTTGAAGCTTTCTGTTGATGTTAACTGAGCTACTAGAGATATTCTTATT 1741 TCACTAAATGTAAAATTTGGAGTAAATATATATGTCAATATTTAGTAAAGCTTTTCTTTT 1801 TTAATTTCCAGGAAAAAATAAAAAGAGTATGAGTCTTCTGTAATTCATTGAGCAGTTAGC 1861 TCATTTGAGATAAAGTCAAATGCCAAACACTAGCTCTGTATTAATCCCCATCATTACTGG 1921 TAAAGCCTCATTTGAATGTGTGAATTCAATACAGGCTATGTAAAATTTTTACTAATGTCA 1981 TTATTTTGAAAAAATAAATTTAAAAATACATTCAAAATTACTATTGTATACAAGCTTAAT 2041 TGTTAATATTCCCTAAACACAATTTTATGAAGGGAGAAGACATTGGTTTGTTGACAATAA 2101 CAGTACATCTTTTCAAGTTCTCAGCTATTTCTTCTACCTCTCCCTATCTTACATTTGAGT 2161 ATGGTAACTTATGTCATCTATGTTGAATGTAAGCTTATAAAGCACAAAGCATACATTTCC 2221 TGACTGGTCTAGAGAACTGATGTTTCAATTTACCCCTCTGCTAAATAAATATTAAAACTA 2281 TCATGTG

[0676] The stop codon is indicated in bold as well as the position corresponding to the microarray probe.

[0677] The corresponding amino acid sequence is given in ENSEMBL accession no. ENSP00000052754 and has a sequence as in SEQ ID NO:492

TABLE-US-00098 1 MKATIILLLLAQVSWAGPFQQRGLFDFMLEDEASGIGPEVPDDRDFEPSLGPVCPFRCQC 61 HLRVVQCSDLGLDKVPKDLPPDTTLLDLQNNKITEIKDGDFKNLKNLHALILVNNKISKV 121 SPGAFTPLVKLERLYLSKNQLKELPEKMPKTLQELRAHENEITKVRKVTFNGLNQMIVIE 181 LGTNPLKSSGIENGAFQGMKKLSYIRIADTNITSIPQGLPPSLTELHLDGNKISRVDAAS 241 LKGLNNLAKLGLSFNSISAVDNGSLANTPHLRELHLDNNKLTRVPGGLAEHKYIQVVYLH 301 NNNISVVGSSDFCPPGHNTKKASYSGVSLFSNPVQYWEIQPSTFRCVYVRSAIQLGNYK

[0678] Primers for amplifying the sequence DCN can be designed using primer design software such as Oligo Calc and/or Primer 3. Examples of primer pairs for amplifying DCN include those in

TABLE-US-00099 Forward SEQ ID NO: 493 AGCTTTGAGGGCTCCTGTG Reverse SEQ ID NO: 494 GCAAGCAGAAGGAGGATGAT Forward SEQ ID NO: 495 AATGCCATCTTCGAGTGGTC Reverse SEQ ID NO: 496 TGCAGGTCTAGCAGAGTTGTG Forward SEQ ID NO: 497 AACCGAAATCAAAGATGGAGA Reverse SEQ ID NO: 498 GTCCAGGTGGGCAGAAGTC Forward SEQ ID NO: 499 AATGCCATCTTCGAGTGGTC Reverse SEQ ID NO: 500 CTGCTGATTTTGTTGCCATC Forward SEQ ID NO: 501 TGGCAACAAAATCAGCAGAG Reverse SEQ ID NO: 502 GCCATTGTCAACAGCAGAGA Forward SEQ ID NO: 503 GGGCTGGCAGAGCATAAGTA Reverse SEQ ID NO: 504 GTCCAGGTGGGCAGAAGTC Forward SEQ ID NO: 505 AACCGAAATCAAAGATGGAGA Reverse SEQ ID NO: 506 CCAAAGGTGTAAATGCTCCAG Forward SEQ ID NO: 507 GAGATCACCAAAGTGCGAAA Reverse SEQ ID NO: 508 AAAGCCCCATTTTCAATTCC Forward SEQ ID NO: 509 AATGCCATCTTCGAGTGGTC Reverse SEQ ID NO: 510 AAAGCCCCATTTTCAATTCC

[0679] Other sets of primers can be readily designed by the skilled artisan and/or are known in the art.

[0680] Probes for detecting DCN can be derived from any number of sources depending on the desired use (e.g., using the above described primers and appropriate reagents). Other examples of probes include

[0681] The probe used on the microarray has a sequence as in

TABLE-US-00100 SEQ ID NO: 511 TTTAACTGTGCTATGGAGTAGAAGCAGGAGGTTTTCAACCTAGTCACAGA GCAGCACC SEQ ID NO: 512 TTCCCGGATTAAAAGGTTCC SEQ ID NO: 513 AAGTGCCAAAGGATCTTCCC SEQ ID NO: 514 CCTGAAGAACCTTCACGTTG SEQ ID NO: 515 TCCTCCTTCCCTTACGGAAT SEQ ID NO: 516 ATGCAGCTAGCCTGAAAGGA SEQ ID NO: 517 CATCCAGGTTGTCTACCTTCA SEQ ID NO: 518 TGAAGAACCTTCACGCATTG SEQ ID NO: 519 TGTCATAGAACTGGGCACCA SEQ ID NO: 520 GTTCTGATTTGGAACTGGGC

[0682] Antibodies to DCN include, but are not limited to, Mouse Anti-Human Decorin Monoclonal Antibody, Unconjugated Cat# ab54728, against recombinant full length protein; and Anti-DCN Monoclonal Antibody, Unconjugated, Clone 2B5-G5 Cat# H00001634-M02, against recombinant full length protein.

[0683] Additional primers for the biomarkers of the invention:

TABLE-US-00101 ACAA 1 SEQ ID NO: 521 tcacgggagaagcaggatac SEQ ID NO: 522 cttgctctgggctcttgc SEQ ID NO: 523 ccagagattgcctgattcct SEQ ID NO: 524 cctgcttctcccgtgaaat SEQ ID NO: 525 agctgggggacatctgtgt SEQ ID NO: 526 cactcagaaactgggcgatt AP1M2 SEQ ID NO: 527 cacatcgaagaatgccaatg SEQ ID NO: 528 gctccttgaagtattcgcaga SEQ ID NO: 529 tgctcttcgagctcactgg SEQ ID NO: 530 cacgcactggtggaatttt SEQ ID NO: 531 gttcgctacatcacccagagt SEQ ID NO: 532 gtaaggaagccccgtgttc CGN SEQ ID NO: 533 gagcttacccgaaaagtgga SEQ ID NO: 534 tctagcttctgccgcttctt SEQ ID NO: 535 ggagatactcgccaggttga SEQ ID NO: 536 ccttaagctcctcctgtgtcc SEQ ID NO: 537 cctctgtgaggaggaaggttag SEQ ID NO: 538 ttagtagaaccagaagaaaccatcac DDR1 SEQ ID NO: 539 tagagagccacccccgta SEQ ID NO: 540 ccatatagtccccactgtaggc SEQ ID NO: 541 ccactctgctccctgtgtc SEQ ID NO: 542 ctggcttctcaggctccata SEQ ID NO: 543 tggggactattaccgtgtgc SEQ ID NO: 544 acgtcactcgcagtcgtg EPS8L2 SEQ ID NO: 545 gcagctcttctccctcaaca SEQ ID NO: 546 cccactttgctgcttctcc SEQ ID NO: 547 caagatgagccccaaggac SEQ ID NO: 548 tgatgacgttggagttggaa SEQ ID NO: 549 caaggatgaggtcctagaggtg SEQ ID NO: 550 gatgttgcagggcacgta FASTKD1 SEQ ID NO: 551 tggaaattctggggtatcgt SEQ ID NO: 552 gcatcctttgttgacagtgc SEQ ID NO: 553 cctgggaatcaaatatcgaaatag SEQ ID NO: 554 ccaaaaattccaaagcaatcc SEQ ID NO: 555 aagaattaacttttctgcatttcca SEQ ID NO: 556 cagaacagacacctcagttggt GMIP SEQ ID NO: 557 aaccctggccatggagac SEQ ID NO: 558 ccgccacttctcaatctcag SEQ ID NO: 559 cccagcaccacagtaccc SEQ ID NO: 560 ctctgtggagttggaatctcg SEQ ID NO: 561 ctggtggcccatctgttc SEQ ID NO: 562 ggttgttggcagacatcttgt IKBKE SEQ ID NO: 563 acagttcaagaagtctaggatgagg SEQ ID NO: 564 tggctaaatgactgaaattcacc SEQ ID NO: 565 ggacatccctcctctacctca SEQ ID NO: 566 ggatctcaggcgttccag SEQ ID NO: 567 ctgcctgaggatgagttcct SEQ ID NO: 568 gatgcacaatgccgttctc P2RX4 SEQ ID NO: 569 ccgttacgaccaaggtcaag SEQ ID NO: 570 tgacgaagagggagttttcc SEQ ID NO: 571 tctgtcaagacgtgtgaggtg SEQ ID NO: 572 agtgaagttttctgcagccttta SEQ ID NO: 573 tctcctggctacaatttcagg SEQ ID NO: 574 atgccataggccttgatgag P4HB SEQ ID NO: 575 gcttcccccaaggaatataca SEQ ID NO: 576 tcttcagccagttcacgatg SEQ ID NO: 577 gcaggggatgatgacgat SEQ ID NO: 578 cgtcttcctccatgtctgg SEQ ID NO: 579 ctggagggcaaaatcaagc SEQ ID NO: 580 ttcttcccaacaagcacctt PHKG2 SEQ ID NO: 581 gcagatccgactttcagatttc SEQ ID NO: 582 ggggtcccacacaactctc SEQ ID NO: 583 ttccagcactgtcaaagacct SEQ ID NO: 584 aaagaaggggtgctgtaggg SEQ ID NO: 585 aggctatggcaaggaggtc SEQ ID NO: 586 tgcgtaacatcaggatctgc PPFIBP2 SEQ ID NO: 587 aggggataaggagtccctca SEQ ID NO: 588 ctggtgtccttccagacaca SEQ ID NO: 589 gaatggaagctaaaggccact SEQ ID NO: 590 atctttcagggccacctgtt SEQ ID NO: 591 aatcttcgagggagtggagtc SEQ ID NO: 592 cagggtgtccccagtgaa PPP1R16A SEQ ID NO: 593 ccctcccagtgttgtcctt SEQ ID NO: 594 ccccactcccaaggaact SEQ ID NO: 595 gagtgctggacgcctctg SEQ ID NO: 596 ttgaccgccaggagattg SEQ ID NO: 597 atgccctatgacctgtgtgat SEQ ID NO: 598 gatgctgtcctgggtgatg RASSF7 SEQ ID NO: 599 cactagcccaagcaataggc

SEQ ID NO: 600 cactcttgtggcagcaactg SEQ ID NO: 601 cagcctggctctggtgag SEQ ID NO: 602 ggagctctcggttcagctc SEQ ID NO: 603 tctgcctccagccagaga SEQ ID NO: 604 ctccaggagttctgcgtcat RNF183 SEQ ID NO: 605 tccagagtagtctgcctgacc SEQ ID NO: 606 catcctcagccacacacg SEQ ID NO: 607 tccagagtagtctgcctgacc SEQ ID NO: 608 tgttgttgaaggggttccag SEQ ID NO: 609 tctgccaccgtgtctacg SEQ ID NO: 610 cggaaacactccctcaaaga SIRT6 SEQ ID NO: 611 agctgagggacaccatccta SEQ ID NO: 612 atgtacccagcgtgatggac SEQ ID NO: 613 aggatgtcggtgaattacgc SEQ ID NO: 614 agaccagcctcgccagtt SEQ ID NO: 615 ggtcagccagaacgtgga SEQ ID NO: 616 gtggagctctgccagtttgt TJP3 SEQ ID NO: 617 gtgggcatcttcgtgtcc SEQ ID NO: 618 gaatggcacgtcattcacc SEQ ID NO: 619 atctggacggcggaagat SEQ ID NO: 620 ggtgagggaggtctaggttgt SEQ ID NO: 621 tcatcaagcacattacagattcg SEQ ID NO: 622 ggctagacaccccgttgat EFEMP2 SEQ ID NO: 623 actcgcagggggacttttac SEQ ID NO: 624 catgagggaattcatggtga SEQ ID NO: 625 atcgggatggcttctcct SEQ ID NO: 626 tgatgcagcggtactgaca SEQ ID NO: 627 agtaccgctgcatcaacga SEQ ID NO: 628 cgcaccagactcacactcat SOCS2 SEQ ID NO: 629 ggagctcggtcagacagg SEQ ID NO: 630 ctaatcaagaaagttccttctggtg SEQ ID NO: 631 cagtcaccaagccccttc SEQ ID NO: 632 aagggatggggctctttct SEQ ID NO: 633 ggagctcggtcagacagg SEQ ID NO: 634 gttccttctggtgcctctttt DCN SEQ ID NO: 635 ggagactttaagaacctgaagaacc SEQ ID NO: 636 cgttccaacttcaccaaagg SEQ ID NO: 637 ctgtcaatgccatcttcgag SEQ ID NO: 638 gatcctttggcactttgtcc SEQ ID NO: 639 caatatcaccagcattcctcaag SEQ ID NO: 640 ctgctgattttgttgccatc

[0684] All publications and patent applications mentioned in the specification are indicative of the level of those skilled in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The mere mentioning of the publications and patent applications does not necessarily constitute an admission that they are prior art to the instant application.

[0685] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be obvious that certain changes and modifications may be practiced within the scope of the appended claims.

Sequence CWU 1

1

64011695DNAHomo Sapiens 1atgtggttct gcgcgtgtgc ggacggctgt ctgttaactc cgcggtcagt tcccggactg 60gtggctggtc tgcagggttg acctgcgcaa tgcagaggct gcaggtagtg ctgggccacc 120tgaggggtcc ggccgattcc ggctggatgc cgcaggccgc gccttgcctg agcggtgccc 180cgcaggcctc ggccgcggac gtggtggtgg tgcacgggcg gcgcacggcc atctgccggg 240cgggccgcgg cggcttcaag gacaccaccc ccgacgagct tctctcggca gtcatgaccg 300cggttctcaa ggacgtgaat ctgaggccgg aacagctggg ggacatctgt gtcggaaatg 360tgctgcagcc tggggccggg gcaatcatgg cccgaatcgc ccagtttctg agtgacatcc 420cggagactgt gcctttgtcc actgtcaata gacagtgttc gtcggggcta caggcagtgg 480ccagcatagc aggtggcatc agaaatgggt cttatgacat tggcatggcc tgtggggtgg 540agtccatgtc cctggctgac agagggaacc ctggaaatat tacttcgcgc ttgatggaga 600aggagaaggc cagagattgc ctgattccta tggggataac ctctgagaat gtggctgagc 660ggtttggcat ttcacgggag aagcaggata cctttgccct ggcttcccag cagaaggcag 720caagagccca gagcaagggc tgtttccaag ctgagattgt gcctgtgacc accacggtcc 780atgatgacaa gggcaccaag aggagcatca ctgtgaccca ggatgagggt atccgcccca 840gcaccaccat ggagggcctg gccaaactga agcctgcctt caagaaagat ggttctacca 900cagctggaaa ctctagccag gtgagtgatg gggcagctgc catcctgctg gcccggaggt 960ccaaggcaga agagttgggc cttcccatcc ttggggtcct gaggtcttat gcagtggttg 1020gggtcccacc tgacatcatg ggcattggac ctgcctatgc catcccagta gctttgcaaa 1080aagcagggct gacagtgagt gacgtggaca tcttcgagat caatgaggcc tttgcaagcc 1140aggctgccta ctgtgtggag aagctacgac tcccccctga gaaggtgaac cccctggggg 1200gtgcagtggc cttagggcac ccactgggct gcactggggc acgacaggtc atcacgctgc 1260tcaatgagct gaagcgccgt gggaagaggg catacggagt ggtgtccatg tgcatcggga 1320ctggaatggg agccgctgcc gtctttgaat accctgggaa ctgagtgagg tcccaggctg 1380gaggcgctac gcagacagtc ctgctgctct agcagcaagg cagtaacacc acaaaagcaa 1440aaccacatgg gaaaactcag cactggtggt ggtggcagtg gacagatcaa ggcacttcaa 1500ctcatttgga aaatgtgaac actgatgaca tggtatagga gtgggtgggg tgttgagcca 1560cccatcagac cctctttagc tgtgcaagat aaaagcagcc tgggtcaccc aggccacaag 1620gccatggtta attcttaagg caaggcaaat ccatggatga gaagtgcaat gggcatagta 1680aaagtgcatg aattt 16952424PRTHomo Sapiens 2Met Gln Arg Leu Gln Val Val Leu Gly His Leu Arg Gly Pro Ala Asp 1 5 10 15 Ser Gly Trp Met Pro Gln Ala Ala Pro Cys Leu Ser Gly Ala Pro Gln 20 25 30 Ala Ser Ala Ala Asp Val Val Val Val His Gly Arg Arg Thr Ala Ile 35 40 45 Cys Arg Ala Gly Arg Gly Gly Phe Lys Asp Thr Thr Pro Asp Glu Leu 50 55 60 Leu Ser Ala Val Met Thr Ala Val Leu Lys Asp Val Asn Leu Arg Pro 65 70 75 80 Glu Gln Leu Gly Asp Ile Cys Val Gly Asn Val Leu Gln Pro Gly Ala 85 90 95 Gly Ala Ile Met Ala Arg Ile Ala Gln Phe Leu Ser Asp Ile Pro Glu 100 105 110 Thr Val Pro Leu Ser Thr Val Asn Arg Gln Cys Ser Ser Gly Leu Gln 115 120 125 Ala Val Ala Ser Ile Ala Gly Gly Ile Arg Asn Gly Ser Tyr Asp Ile 130 135 140 Gly Met Ala Cys Gly Val Glu Ser Met Ser Leu Ala Asp Arg Gly Asn 145 150 155 160 Pro Gly Asn Ile Thr Ser Arg Leu Met Glu Lys Glu Lys Ala Arg Asp 165 170 175 Cys Leu Ile Pro Met Gly Ile Thr Ser Glu Asn Val Ala Glu Arg Phe 180 185 190 Gly Ile Ser Arg Glu Lys Gln Asp Thr Phe Ala Leu Ala Ser Gln Gln 195 200 205 Lys Ala Ala Arg Ala Gln Ser Lys Gly Cys Phe Gln Ala Glu Ile Val 210 215 220 Pro Val Thr Thr Thr Val His Asp Asp Lys Gly Thr Lys Arg Ser Ile 225 230 235 240 Thr Val Thr Gln Asp Glu Gly Ile Arg Pro Ser Thr Thr Met Glu Gly 245 250 255 Leu Ala Lys Leu Lys Pro Ala Phe Lys Lys Asp Gly Ser Thr Thr Ala 260 265 270 Gly Asn Ser Ser Gln Val Ser Asp Gly Ala Ala Ala Ile Leu Leu Ala 275 280 285 Arg Arg Ser Lys Ala Glu Glu Leu Gly Leu Pro Ile Leu Gly Val Leu 290 295 300 Arg Ser Tyr Ala Val Val Gly Val Pro Pro Asp Ile Met Gly Ile Gly 305 310 315 320 Pro Ala Tyr Ala Ile Pro Val Ala Leu Gln Lys Ala Gly Leu Thr Val 325 330 335 Ser Asp Val Asp Ile Phe Glu Ile Asn Glu Ala Phe Ala Ser Gln Ala 340 345 350 Ala Tyr Cys Val Glu Lys Leu Arg Leu Pro Pro Glu Lys Val Asn Pro 355 360 365 Leu Gly Gly Ala Val Ala Leu Gly His Pro Leu Gly Cys Thr Gly Ala 370 375 380 Arg Gln Val Ile Thr Leu Leu Asn Glu Leu Lys Arg Arg Gly Lys Arg 385 390 395 400 Ala Tyr Gly Val Val Ser Met Cys Ile Gly Thr Gly Met Gly Ala Ala 405 410 415 Ala Val Phe Glu Tyr Pro Gly Asn 420 320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 3gagcttctct cggcagtcat 20419DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 4ctcagaaact gggcgattc 19518DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 5gcaatcatgg cccgaatc 18620DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 6ccccgacgaa cactgtctat 20720DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 7gtgcctttgt ccactgtcaa 20818DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 8acaggccatg ccaatgtc 18920DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 9tcacgggaga agcaggatac 201020DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 10ctcttggtgc ccttgtcatc 201120DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 11ggctgacagt gagtgacgtg 201219DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 12agggggttca ccttctcag 191320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 13gtggcatcag aaatgggtct 201420DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 14ctctggcctt ctccttctcc 201520DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 15attacttcgc gcttgatgga 201620DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 16agggcaaagg tatcctgctt 201720DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 17gcctgccttc aagaaagatg 201820DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 18taagacctca ggaccccaag 201920DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 19tggggtcctg aggtcttatg 202020DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 20tctcgaagat gtccacgtca 202120DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 21gtggcatcag aaatgggtct 202220DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 22agggcaaagg tatcctgctt 202320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 23tgacccagga tgagggtatc 202420DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 24tctcgaagat gtccacgtca 202520DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding ACAA1 protein" 25ggagactgtg cctttgtcca 202619DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding ACAA1 protein" 26ctctgtcagc cagggacat 192720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 27cggttctcaa ggacgtgaat 202820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 28agtgacatcc cggagactgt 202920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 29gtggcatcag aaatgggtct 203020DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 30agctgagatt gtgcctgtga 203120DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 31atcaatgagg cctttgcaag 203220DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 32acagagggaa ccctggaaat 203320DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 33gattgcctga ttcctatggg 203420DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 34gtccaaggca gaagagttgg 203520DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 35atgccatccc agtagctttg 203620DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 36gcctgtggga taacctctga 203720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 37aaactgaagc ctgccttcaa 203820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 38atagacagtg ttcgtcgggg 203960DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding ACAA1 protein" 39gctacgcaga cagtcctgct gctctagcag caaggcagta acaccacaaa agcaaaacca 60401749DNAHomo Sapiens 40ggcgcttccg caggaagaag gaagcggcgc cgccatcgcc tcccggcgct ccctccccga 60ctcctaagtc cttcggccgc caccatgtcc gcctcggctg tcttcattct ggacgttaag 120ggcaagccat tgatcagccg caactacaag ggcgatgtgg ccatgagcaa gattgagcac 180ttcatgcctt tgctggtaca gcgggaggag gaaggcgccc tggccccgct gctgagccac 240ggccaggtcc acttcctatg gatcaaacac agcaacctct acttggtggc caccacatcg 300aagaatgcca atgcctccct ggtgtactcc ttcctgtata agacaataga ggtattctgc 360gaatacttca aggagctgga ggaggagagc atccgggaca actttgtcat cgtctacgag 420ttgctggacg agctcatgga ctttggcttc ccgcagacca ccgacagcaa gatcctgcag 480gagtacatca ctcagcagag caacaagctg gagacgggca agtcacgggt gccacccact 540gtcaccaacg ctgtgtcctg gcgctccgag ggtatcaagt ataagaagaa cgaggtcttc 600attgatgtca tagagtctgt caacctgctg gtcaatgcca acggcagcgt ccttctgagc 660gaaatcgtcg gtaccatcaa gctcaaggtg tttctgtcag gaatgccaga gctgcggctg 720ggcctcaatg accgcgtgct cttcgagctc actggccgca gcaagaacaa atcagtagag 780ctggaggatg taaaattcca ccagtgcgtg cggctctctc gctttgacaa cgaccgcacc 840atctccttca tcccgcctga tggtgacttt gagctcatgt cataccgcct cagcacccag 900gtcaagccac tgatctggat tgagtctgtc attgagaagt tctcccacag ccgcgtggag 960atcatggtca aggccaaggg gcagtttaag aaacagtcag tggccaacgg tgtggagata 1020tctgtgcctg tacccagcga tgccgactcc cccagattca agaccagtgt gggcagcgcc 1080aagtatgtgc cggagagaaa cgtcgtgatt tggagtatta agtctttccc ggggggcaag 1140gagtacttga tgcgagccca ctttggcctc cccagtgtgg aaaaggaaga ggtggagggc 1200cggcccccca tcggggtcaa gtttgagatc ccctacttca ccgtctctgg gatccaggtc 1260cgatacatga agatcattga gaaaagtggt taccaggccc tgccctgggt tcgctacatc 1320acccagagtg gcgattacca acttcgtacc agctagaagg gagaagagat gggggcttga 1380acacggggct tccttacagc cccggatgca gattttagag ggagggcagg tgcgggctgt 1440gtgtgtctgt gtgagggcag gtcctggact tggcagtttc ttgctcccag cacccgcccc 1500ttcctcacct cttccttatt ccataggctg ggagagaaac tctctgcttc cctcgccctt 1560ggagctttcc ccatccccct gattttatat gaagaaatag aagaggggct tgaagtcccc 1620ctcgcgagtg ccttcttgca attacctgcc ttagcgggtg ttgcgggtcc ctccttcaca 1680gccgctgagc ccagaggtcc cgctggcccc tcctctgaat tttaggatgt cattaaaaag 1740atgaatcta 174941423PRTHomo Sapiens 41Met Ser Ala Ser Ala Val Phe Ile Leu Asp Val Lys Gly Lys Pro Leu 1 5 10 15 Ile Ser Arg Asn Tyr Lys Gly Asp Val Ala Met Ser Lys Ile Glu His 20 25 30 Phe Met Pro Leu Leu Val Gln Arg Glu Glu Glu Gly Ala Leu Ala Pro 35 40 45 Leu Leu Ser His Gly Gln Val His Phe Leu Trp Ile Lys His Ser Asn 50 55 60 Leu Tyr Leu Val Ala Thr Thr Ser Lys Asn Ala Asn Ala Ser Leu Val 65 70 75 80 Tyr Ser Phe Leu Tyr

Lys Thr Ile Glu Val Phe Cys Glu Tyr Phe Lys 85 90 95 Glu Leu Glu Glu Glu Ser Ile Arg Asp Asn Phe Val Ile Val Tyr Glu 100 105 110 Leu Leu Asp Glu Leu Met Asp Phe Gly Phe Pro Gln Thr Thr Asp Ser 115 120 125 Lys Ile Leu Gln Glu Tyr Ile Thr Gln Gln Ser Asn Lys Leu Glu Thr 130 135 140 Gly Lys Ser Arg Val Pro Pro Thr Val Thr Asn Ala Val Ser Trp Arg 145 150 155 160 Ser Glu Gly Ile Lys Tyr Lys Lys Asn Glu Val Phe Ile Asp Val Ile 165 170 175 Glu Ser Val Asn Leu Leu Val Asn Ala Asn Gly Ser Val Leu Leu Ser 180 185 190 Glu Ile Val Gly Thr Ile Lys Leu Lys Val Phe Leu Ser Gly Met Pro 195 200 205 Glu Leu Arg Leu Gly Leu Asn Asp Arg Val Leu Phe Glu Leu Thr Gly 210 215 220 Arg Ser Lys Asn Lys Ser Val Glu Leu Glu Asp Val Lys Phe His Gln 225 230 235 240 Cys Val Arg Leu Ser Arg Phe Asp Asn Asp Arg Thr Ile Ser Phe Ile 245 250 255 Pro Pro Asp Gly Asp Phe Glu Leu Met Ser Tyr Arg Leu Ser Thr Gln 260 265 270 Val Lys Pro Leu Ile Trp Ile Glu Ser Val Ile Glu Lys Phe Ser His 275 280 285 Ser Arg Val Glu Ile Met Val Lys Ala Lys Gly Gln Phe Lys Lys Gln 290 295 300 Ser Val Ala Asn Gly Val Glu Ile Ser Val Pro Val Pro Ser Asp Ala 305 310 315 320 Asp Ser Pro Arg Phe Lys Thr Ser Val Gly Ser Ala Lys Tyr Val Pro 325 330 335 Glu Arg Asn Val Val Ile Trp Ser Ile Lys Ser Phe Pro Gly Gly Lys 340 345 350 Glu Tyr Leu Met Arg Ala His Phe Gly Leu Pro Ser Val Glu Lys Glu 355 360 365 Glu Val Glu Gly Arg Pro Pro Ile Gly Val Lys Phe Glu Ile Pro Tyr 370 375 380 Phe Thr Val Ser Gly Ile Gln Val Arg Tyr Met Lys Ile Ile Glu Lys 385 390 395 400 Ser Gly Tyr Gln Ala Leu Pro Trp Val Arg Tyr Ile Thr Gln Ser Gly 405 410 415 Asp Tyr Gln Leu Arg Thr Ser 420 4223DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding AP1M2 protein" 42cgccaccatg tccgcctcgg ctg 234322DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding AP1M2 protein" 43gctcaatctt gctcatggcc ac 224421DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding AP1M2 protein" 44caggtccact tcctatggat c 214520DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding AP1M2 protein" 45caaagttgtc ccggatgctc 204618DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding AP1M2 protein" 46cgctccgagg gtatcaag 184719DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding AP1M2 protein" 47cttgctgcgg ccagtgagc 194822DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding AP1M2 protein" 48gactttgagc tcatgtcata cc 224922DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding AP1M2 protein" 49cttaatactc caaatcacga cg 225019DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding AP1M2 protein" 50gtttgagatc ccctacttc 195124DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding AP1M2 protein" 51gcctggtaac cacttttctc aatg 245219DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding AP1M2 protein" 52ctgggttcgc tacatcacc 195315DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding AP1M2 protein" 53gccccgtgtt caagc 155419DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding AP1M2 protein" 54catgcctttg ctggtacag 195521DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding AP1M2 protein" 55gagtacacca gggaggcatt g 215619DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding AP1M2 protein" 56ctccctggtg tactccttc 195722DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding AP1M2 protein" 57gctgtcggtg gtctgcggga ag 225819DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding AP1M2 protein" 58cagcaagatc ctgcaggag 195919DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding AP1M2 protein" 59caggttgaca gactctatg 196060DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding AP1M2 protein" 60atgaagaaat agaagagggg cttgaagtcc tcctcgcgag tgccttcttg caattacctg 606158DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding AP1M2 protein" 61ccaggtccac ttcctatgga tcaaacacag caacctctac ttggtggcca ccacatcg 586243DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding AP1M2 protein" 62gacaatagag gtattctgcg aatacttcaa ggagctggag gag 436354DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding AP1M2 protein" 63caatgaccgc gtgctcttcg agctcactgg ccgcagcaag aacaaatcag taga 546456DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding AP1M2 protein" 64tttcccgggg ggcaaggagt acttgatgcg agcccacttt ggcctcccca gtgtgg 56655132DNAHomo Sapiens 65gagggagctc cgaggacgag ggggagggcc ggagctgcgc gtgctgcttt gcccgagccc 60gagcccgagc ccgagcccga gcccgagccc gagcccgaac gcaagcctgg gagcgcggag 120cccggctagg gactcctcct atttatggag caggcaccca acatggctga gccccggggc 180cccgtagacc atggagtcca gattcgcttc atcacagagc cagtgagtgg tgcagagatg 240ggcactctac gtcgaggtgg acgacgccca gctaaggatg caagagccag tacctacggg 300gttgctgtgc gtgtgcaggg aatcgctggg cagccctttg tggtgctcaa cagtggggag 360aaaggcggtg actcctttgg ggtccaaatc aagggggcca atgaccaagg ggcctcagga 420gctctgagct cagatttgga actccctgag aacccctact ctcaggtcaa gggatttcct 480gccccctcgc agagcagcac atctgatgag gagcctgggg cctactggaa tggaaagcta 540ctccgttccc actcccaggc ctcactggca ggccctggcc cagtggatcc tagtaacaga 600agcaacagca tgctggagct agccccgaaa gtggcttccc caggtagcac cattgacact 660gctcccctgt cttcagtgga ctcactcatc aacaagtttg acagtcaact tggaggccag 720gcccggggtc ggactggccg ccgaacacgg atgctacccc ctgaacagcg caaacggagc 780aagagcctgg acagccgcct cccacgggac acctttgagg aacgggagcg ccagtccacc 840aaccactgga cctctagcac aaaatatgac aaccatgtgg gcacttcgaa gcagccagcc 900cagagccaga acctgagtcc tctcagtggc tttagccgtt ctcgtcagac tcaggactgg 960gtccttcaga gttttgagga gccgcggagg agtgcacagg accccaccat gctgcagttc 1020aaatcaactc cagacctcct tcgagaccag caggaggcag ccccaccagg cagtgtggac 1080catatgaagg ccaccatcta tggcatcctg agggagggaa gctcagaaag tgaaacctct 1140gtgaggagga aggttagttt ggtgctggag aagatgcagc ctctagtgat ggtttcttct 1200ggttctacta aggccgtggc agggcagggt gagcttaccc gaaaagtgga ggagctacag 1260cgaaagctgg atgaagaggt gaagaagcgg cagaagctag agccatccca agttgggctg 1320gagcggcagc tggaggagaa aacagaagag tgcagccgac tgcaggagct gctggagagg 1380aggaaggggg aggcccagca gagcaacaag gagctccaga acatgaagcg cctcttggac 1440cagggtgaag atttacgaca tgggctggag acccaggtga tggagctgca gaacaagctg 1500aaacatgtcc agggtcctga gcctgctaag gaggtgttac tgaaggacct gttagagacc 1560cgggaacttc tggaagaggt cttggagggg aaacagcgag tagaggagca gctgaggctg 1620cgggagcggg agttgacagc cctgaagggg gccctgaaag aggaggtagc ctcccgtgac 1680caggaggtgg aacatgtccg gcagcagtac cagcgagaca cagagcagct ccgcaggagc 1740atgcaagatg caacccagga ccatgcagtg ctggaggccg agaggcagaa gatgtcagcc 1800cttgtgcgag ggctgcagag ggagctggag gagacttcag aggagacagg gcattggcag 1860agtatgttcc agaagaacaa ggaggatctt agagccacca agcaggaact cctgcagctg 1920cgaatggaga aggaggagat ggaagaggag cttggagaga agatagaggt cttgcagagg 1980gaattagagc aggcccgagc tagtgctgga gatactcgcc aggttgaggt gctcaagaag 2040gagctgctcc ggacacagga ggagcttaag gaactgcagg cagaacggca gagccaggag 2100gtggctgggc gacaccggga ccgggagttg gagaagcagc tggcggtcct gagggtcgag 2160gctgatcgag gtcgggagct ggaagaacag aacctccagc tacaaaagac cctccagcaa 2220ctgcgacagg actgtgaaga ggcttccaag gctaagatgg tggccgaggc agaggcaaca 2280gtgctggggc agcggcgggc cgcagtggag acgacgcttc gggagaccca ggaggaaaat 2340gacgaattcc gccggcgcat cctgggtttg gagcagcagc tgaaggagac tcgaggtctg 2400gtggatggtg gggaagcggt ggaggcacga ctacgggaca agctgcagcg gctggaggca 2460gagaaacagc agctggagga ggccctgaat gcgtcccagg aagaggaggg gagtctggca 2520gcagccaagc gggcactgga ggcacgccta gaggaggctc agcgggggct ggcccgcctg 2580gggcaggagc agcagacact gaaccgggcc ctggaggagg aagggaagca gcgggaggtg 2640ctccggcgag gcaaggctga gctggaggag cagaagcgtt tgctggacag gactgtggac 2700cgactgaaca aggagttgga gaagatcggg gaggactcta agcaagccct gcagcagctc 2760caggcccagc tggaggatta taaggaaaag gcccggcggg aggtggcaga tgcccagcgc 2820caggccaagg attgggccag tgaggctgag aagacctctg gaggactgag ccgacttcag 2880gatgagatcc agaggctgcg gcaggccctg caggcatccc aggctgagcg ggacacagcc 2940cggctggaca aagagctact ggcccagcga ctgcaggggc tggagcaaga ggcagagaac 3000aagaagcgtt cccaggacga cagggcccgg cagctgaagg gtctcgagga aaaagtctca 3060cggctggaaa cagagttaga tgaggagaag aacaccgtgg agctgctaac agatcgggtg 3120aatcgtggcc gggaccaggt ggatcagctg aggacagagc tcatgcagga aaggtctgct 3180cggcaggacc tggagtgtga caaaatctcc ttggagagac agaacaagga cctgaagacc 3240cggttggcca gctcagaagg cttccagaag cctagtgcca gcctctctca gcttgagtcc 3300cagaatcagt tgttgcagga gcggctacag gctgaagaga gggagaagac agttctgcag 3360tctaccaatc gaaaactgga gcggaaagtt aaagaactat ccatccagat tgaagacgag 3420cggcagcatg tcaatgacca gaaagaccag ctaagcctga gggtgaaggc tttgaagcgt 3480caggtggatg aagcagaaga ggaaattgag cgactggacg gcctgaggaa gaaggcccag 3540cgtgaggtgg aggagcagca tgaggtcaat gaacagctcc aggcccggat caagtctctg 3600gagaaggact cctggcgcaa agcttcccgc tcagctgctg agtcagctct caaaaacgaa 3660gggctgagct cagatgagga attcgacagt gtctacgatc cctcgtccat tgcatcactg 3720cttacggaga gcaacctaca gaccagctcc tgttagctcg tggtcctcaa ggactcagaa 3780accaggctcg aggcctatcc cagcaagtgc tgctctgctc tgcccaccct gggttctgca 3840ttcctatggg tgacccaatt attcagacct aagacaggga ggggtcagag tgatggtgat 3900aaaaaaaaaa aatcatcagc aataagctga tagatggact ttccactgta ggagtggaca 3960tttcaagcca actgagcctt ttcctcaagt gccgacacct ccctcatctc tcttatagtg 4020gaaggatggt cagcattagg ctgatgggga ctgagaagga taggaaggga tagaaattgc 4080catgtgtata aagctttatt ctttagccct taaccctaag gctcagggaa ataccctatg 4140ttattgtgct ccctggattc ctgcaactca ttttccttcc actctggagc agggtgaggg 4200gaatgttatg ggtaacagac atgcaggcat ggctctaccc atttctttgc acaagtatgg 4260ggcccatgtg gtagtcccca tacccctcca gttcctatat ttttgtcttc ttcctttccc 4320ctctttgcca ttcctacctt gcatttttcc tgtcagtgcc ttagccaagg caaggagata 4380aggatgctct tcttgctttt tatatctgca cattcatacc tctccaaaga ccagcttttc 4440cccagccagg gccctcagcc ttccctgctg ccccagtgat tgattgagag agctgttggg 4500gtttctctgc caatgacccc tgggagaggg actttggtag ggtcatgata aagtggcggg 4560ggtctggtcc tgctcagggt tttcatcctt cctcctctcc ctcctctgtg actgtggata 4620tggttataag gtggttgcac ctgggagccc tgacaactgg ctgcacaaat tccaaaagta 4680aaggtgtcag tccctgtggc cttccttggg gcttctctga ccacatgtgc ccaacttcaa 4740taagagaacc aagggaccct cattttctga ggtgcttggc tctgattcag ggctttgcaa 4800ggggttagaa gctgactgta aaaatgggaa gaggcaacgg aagacattta tttctccttt 4860ggattttggg gagaaccaag ccctggtagg gaagaggtaa gggggatgat tcacctccat 4920atttcctaag caggttgtat agggagccgg tggcaggagg aaggctgttt tcacaaatga 4980cttgtaatgt cgtgattaaa aaaattccta tattcttctg caaatcaaac gttctttccc 5040aatccaatcc agccttggtt ttattttaaa ttaaatatta aaattacaca tttatattga 5100aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 5132661203PRTHomo Sapiens 66Met Glu Gln Ala Pro Asn Met Ala Glu Pro Arg Gly Pro Val Asp His 1 5 10 15 Gly Val Gln Ile Arg Phe Ile Thr Glu Pro Val Ser Gly Ala Glu Met 20 25 30 Gly Thr Leu Arg Arg Gly Gly Arg Arg Pro Ala Lys Asp Ala Arg Ala 35 40 45 Ser Thr Tyr Gly Val Ala Val Arg Val Gln Gly Ile Ala Gly Gln Pro 50 55 60 Phe Val Val Leu Asn Ser Gly Glu Lys Gly Gly Asp Ser Phe Gly Val 65 70 75 80 Gln Ile Lys Gly Ala Asn Asp Gln Gly Ala Ser Gly Ala Leu Ser Ser 85 90 95 Asp Leu Glu Leu Pro Glu Asn Pro Tyr Ser Gln Val Lys Gly Phe Pro 100 105 110 Ala Pro Ser Gln Ser Ser Thr Ser Asp Glu Glu Pro Gly Ala Tyr Trp 115 120 125 Asn Gly Lys Leu Leu Arg Ser His Ser Gln Ala Ser Leu Ala Gly Pro 130 135 140 Gly Pro Val Asp Pro Ser Asn Arg Ser Asn Ser Met Leu Glu Leu Ala 145 150 155 160 Pro Lys Val Ala Ser Pro Gly Ser Thr Ile Asp Thr Ala Pro Leu Ser 165 170 175 Ser Val Asp Ser Leu Ile Asn Lys Phe Asp Ser Gln Leu Gly Gly Gln 180 185 190 Ala Arg Gly Arg Thr Gly Arg Arg Thr Arg Met Leu Pro Pro Glu Gln 195 200 205 Arg Lys Arg Ser Lys Ser Leu Asp Ser Arg Leu Pro Arg Asp Thr Phe 210 215 220 Glu Glu Arg Glu Arg Gln Ser Thr Asn His Trp Thr Ser Ser Thr Lys 225 230 235 240 Tyr Asp Asn His Val Gly Thr Ser Lys Gln Pro Ala Gln Ser Gln Asn 245 250 255 Leu Ser Pro Leu Ser Gly Phe Ser Arg Ser Arg Gln Thr Gln Asp Trp 260 265 270 Val Leu Gln Ser Phe Glu Glu Pro Arg Arg Ser Ala Gln Asp Pro Thr 275 280 285 Met Leu Gln Phe Lys Ser Thr Pro Asp Leu Leu Arg Asp Gln Gln Glu 290 295 300 Ala Ala Pro Pro Gly Ser Val Asp His Met Lys Ala Thr Ile Tyr Gly 305 310 315 320 Ile Leu Arg Glu Gly Ser Ser Glu Ser Glu Thr Ser Val Arg Arg Lys 325 330 335 Val Ser Leu Val Leu Glu Lys Met Gln Pro Leu Val Met Val Ser Ser 340 345 350 Gly Ser Thr Lys Ala Val Ala Gly Gln Gly Glu Leu Thr Arg Lys Val 355 360 365 Glu Glu Leu Gln Arg Lys Leu Asp Glu Glu Val Lys Lys Arg Gln Lys 370 375 380 Leu Glu Pro Ser Gln Val Gly Leu Glu Arg Gln Leu Glu Glu Lys Thr 385 390 395 400 Glu Glu Cys Ser Arg Leu Gln Glu Leu Leu Glu Arg Arg Lys Gly Glu 405 410

415 Ala Gln Gln Ser Asn Lys Glu Leu Gln Asn Met Lys Arg Leu Leu Asp 420 425 430 Gln Gly Glu Asp Leu Arg His Gly Leu Glu Thr Gln Val Met Glu Leu 435 440 445 Gln Asn Lys Leu Lys His Val Gln Gly Pro Glu Pro Ala Lys Glu Val 450 455 460 Leu Leu Lys Asp Leu Leu Glu Thr Arg Glu Leu Leu Glu Glu Val Leu 465 470 475 480 Glu Gly Lys Gln Arg Val Glu Glu Gln Leu Arg Leu Arg Glu Arg Glu 485 490 495 Leu Thr Ala Leu Lys Gly Ala Leu Lys Glu Glu Val Ala Ser Arg Asp 500 505 510 Gln Glu Val Glu His Val Arg Gln Gln Tyr Gln Arg Asp Thr Glu Gln 515 520 525 Leu Arg Arg Ser Met Gln Asp Ala Thr Gln Asp His Ala Val Leu Glu 530 535 540 Ala Glu Arg Gln Lys Met Ser Ala Leu Val Arg Gly Leu Gln Arg Glu 545 550 555 560 Leu Glu Glu Thr Ser Glu Glu Thr Gly His Trp Gln Ser Met Phe Gln 565 570 575 Lys Asn Lys Glu Asp Leu Arg Ala Thr Lys Gln Glu Leu Leu Gln Leu 580 585 590 Arg Met Glu Lys Glu Glu Met Glu Glu Glu Leu Gly Glu Lys Ile Glu 595 600 605 Val Leu Gln Arg Glu Leu Glu Gln Ala Arg Ala Ser Ala Gly Asp Thr 610 615 620 Arg Gln Val Glu Val Leu Lys Lys Glu Leu Leu Arg Thr Gln Glu Glu 625 630 635 640 Leu Lys Glu Leu Gln Ala Glu Arg Gln Ser Gln Glu Val Ala Gly Arg 645 650 655 His Arg Asp Arg Glu Leu Glu Lys Gln Leu Ala Val Leu Arg Val Glu 660 665 670 Ala Asp Arg Gly Arg Glu Leu Glu Glu Gln Asn Leu Gln Leu Gln Lys 675 680 685 Thr Leu Gln Gln Leu Arg Gln Asp Cys Glu Glu Ala Ser Lys Ala Lys 690 695 700 Met Val Ala Glu Ala Glu Ala Thr Val Leu Gly Gln Arg Arg Ala Ala 705 710 715 720 Val Glu Thr Thr Leu Arg Glu Thr Gln Glu Glu Asn Asp Glu Phe Arg 725 730 735 Arg Arg Ile Leu Gly Leu Glu Gln Gln Leu Lys Glu Thr Arg Gly Leu 740 745 750 Val Asp Gly Gly Glu Ala Val Glu Ala Arg Leu Arg Asp Lys Leu Gln 755 760 765 Arg Leu Glu Ala Glu Lys Gln Gln Leu Glu Glu Ala Leu Asn Ala Ser 770 775 780 Gln Glu Glu Glu Gly Ser Leu Ala Ala Ala Lys Arg Ala Leu Glu Ala 785 790 795 800 Arg Leu Glu Glu Ala Gln Arg Gly Leu Ala Arg Leu Gly Gln Glu Gln 805 810 815 Gln Thr Leu Asn Arg Ala Leu Glu Glu Glu Gly Lys Gln Arg Glu Val 820 825 830 Leu Arg Arg Gly Lys Ala Glu Leu Glu Glu Gln Lys Arg Leu Leu Asp 835 840 845 Arg Thr Val Asp Arg Leu Asn Lys Glu Leu Glu Lys Ile Gly Glu Asp 850 855 860 Ser Lys Gln Ala Leu Gln Gln Leu Gln Ala Gln Leu Glu Asp Tyr Lys 865 870 875 880 Glu Lys Ala Arg Arg Glu Val Ala Asp Ala Gln Arg Gln Ala Lys Asp 885 890 895 Trp Ala Ser Glu Ala Glu Lys Thr Ser Gly Gly Leu Ser Arg Leu Gln 900 905 910 Asp Glu Ile Gln Arg Leu Arg Gln Ala Leu Gln Ala Ser Gln Ala Glu 915 920 925 Arg Asp Thr Ala Arg Leu Asp Lys Glu Leu Leu Ala Gln Arg Leu Gln 930 935 940 Gly Leu Glu Gln Glu Ala Glu Asn Lys Lys Arg Ser Gln Asp Asp Arg 945 950 955 960 Ala Arg Gln Leu Lys Gly Leu Glu Glu Lys Val Ser Arg Leu Glu Thr 965 970 975 Glu Leu Asp Glu Glu Lys Asn Thr Val Glu Leu Leu Thr Asp Arg Val 980 985 990 Asn Arg Gly Arg Asp Gln Val Asp Gln Leu Arg Thr Glu Leu Met Gln 995 1000 1005 Glu Arg Ser Ala Arg Gln Asp Leu Glu Cys Asp Lys Ile Ser Leu 1010 1015 1020 Glu Arg Gln Asn Lys Asp Leu Lys Thr Arg Leu Ala Ser Ser Glu 1025 1030 1035 Gly Phe Gln Lys Pro Ser Ala Ser Leu Ser Gln Leu Glu Ser Gln 1040 1045 1050 Asn Gln Leu Leu Gln Glu Arg Leu Gln Ala Glu Glu Arg Glu Lys 1055 1060 1065 Thr Val Leu Gln Ser Thr Asn Arg Lys Leu Glu Arg Lys Val Lys 1070 1075 1080 Glu Leu Ser Ile Gln Ile Glu Asp Glu Arg Gln His Val Asn Asp 1085 1090 1095 Gln Lys Asp Gln Leu Ser Leu Arg Val Lys Ala Leu Lys Arg Gln 1100 1105 1110 Val Asp Glu Ala Glu Glu Glu Ile Glu Arg Leu Asp Gly Leu Arg 1115 1120 1125 Lys Lys Ala Gln Arg Glu Val Glu Glu Gln His Glu Val Asn Glu 1130 1135 1140 Gln Leu Gln Ala Arg Ile Lys Ser Leu Glu Lys Asp Ser Trp Arg 1145 1150 1155 Lys Ala Ser Arg Ser Ala Ala Glu Ser Ala Leu Lys Asn Glu Gly 1160 1165 1170 Leu Ser Ser Asp Glu Glu Phe Asp Ser Val Tyr Asp Pro Ser Ser 1175 1180 1185 Ile Ala Ser Leu Leu Thr Glu Ser Asn Leu Gln Thr Ser Ser Cys 1190 1195 1200 6719DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding CGN protein" 67gctttagccg ttctcgtca 196820DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding CGN protein" 68ctggtctcga aggaggtctg 206920DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding CGN protein" 69cagacctcct tcgagaccag 207021DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding CGN protein" 70ttcctcctca cagaggtttc a 217120DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding CGN protein" 71tacagcgaaa gctggatgaa 207220DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding CGN protein" 72agtcggctgc actcttctgt 207320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding CGN protein" 73tgcagaacaa gctgaaacat 207420DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding CGN protein" 74gctgctcctc tactcgctgt 207520DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding CGN protein" 75gggcattggc agagtatgtt 207620DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding CGN protein" 76ttccatctcc tccttctcca 207719DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding CGN protein" 77cagcaactgc gacaggact 197820DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding CGN protein" 78cattttcctc ctgggtctcc 207920DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding CGN protein" 79ctgagctgga ggagcagaag 208020DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding CGN protein" 80tgcagggctt gcttagagtc 208120DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding CGN protein" 81tggagcaaga ggcagagaac 208220DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding CGN protein" 82actctgtttc cagccgtgag 208320DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding CGN protein" 83caggactggg tccttcagag 208420DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding CGN protein" 84caggcagtgt ggaccatatg 208520DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding CGN protein" 85gctagagcca tcccaagttg 208620DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding CGN protein" 86tgagcctgct aaggaggtgt 208720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding CGN protein" 87tagagccacc aagcaggaac 208820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding CGN protein" 88ttccaaggct aagatggtgg 208920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding CGN protein" 89gacaggactg tggaccgact 209020DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding CGN protein" 90tgaagggtct cgaggaaaaa 209160DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding CGN protein" 91gggaagaggt aagggggatg attcacctcc atatttccta agcaggttgt atagggagcc 60924838DNAHomo Sapiens 92gtcttcccct cgtgggccct gagcgggact gcagccagcc ccctggggcg ccagctttga 60ggcccccgac agctgctctc gggagccgcc tcccgacacc cgagccccgc cggcgcctcc 120cgctcccggc tcccggctcc tggctccctc cgcctccccc gcccctcgcc ccgccgccaa 180gaggccccgc tcccgggtcg gacgcctggg tctgccggga agagcgatga gaggtgtctg 240aaggtggcta ttcactgagc gatggggttg gacttgaagg aatgccaaga gatgctgccc 300ccaccccctt aggcccgagg gatcaggagc tatgggacca gaggccctgt catctttact 360gctgctgctc ttggtggcaa gtggagatgc tgacatgaag ggacattttg atcctgccaa 420gtgccgctat gccctgggca tgcaggaccg gaccatccca gacagtgaca tctctgcttc 480cagctcctgg tcagattcca ctgccgcccg ccacagcagg ttggagagca gtgacgggga 540tggggcctgg tgccccgcag ggtcggtgtt tcccaaggag gaggagtact tgcaggtgga 600tctacaacga ctgcacctgg tggctctggt gggcacccag ggacggcatg ccgggggcct 660gggcaaggag ttctcccgga gctaccggct gcgttactcc cgggatggtc gccgctggat 720gggctggaag gaccgctggg gtcaggaggt gatctcaggc aatgaggacc ctgagggagt 780ggtgctgaag gaccttgggc cccccatggt tgcccgactg gttcgcttct acccccgggc 840tgaccgggtc atgagcgtct gtctgcgggt agagctctat ggctgcctct ggagggatgg 900actcctgtct tacaccgccc ctgtggggca gacaatgtat ttatctgagg ccgtgtacct 960caacgactcc acctatgacg gacataccgt gggcggactg cagtatgggg gtctgggcca 1020gctggcagat ggtgtggtgg ggctggatga ctttaggaag agtcaggagc tgcgggtctg 1080gccaggctat gactatgtgg gatggagcaa ccacagcttc tccagtggct atgtggagat 1140ggagtttgag tttgaccggc tgagggcctt ccaggctatg caggtccact gtaacaacat 1200gcacacgctg ggagcccgtc tgcctggcgg ggtggaatgt cgcttccggc gtggccctgc 1260catggcctgg gagggggagc ccatgcgcca caacctaggg ggcaacctgg gggaccccag 1320agcccgggct gtctcagtgc cccttggcgg ccgtgtggct cgctttctgc agtgccgctt 1380cctctttgcg gggccctggt tactcttcag cgaaatctcc ttcatctctg atgtggtgaa 1440caattcctct ccggcactgg gaggcacctt cccgccagcc ccctggtggc cgcctggccc 1500acctcccacc aacttcagca gcttggagct ggagcccaga ggccagcagc ccgtggccaa 1560ggccgagggg agcccgaccg ccatcctcat cggctgcctg gtggccatca tcctgctcct 1620gctgctcatc attgccctca tgctctggcg gctgcactgg cgcaggctcc tcagcaaggc 1680tgaacggagg gtgttggaag aggagctgac ggttcacctc tctgtccctg gggacactat 1740cctcatcaac aaccgcccag gtcctagaga gccacccccg taccaggagc cccggcctcg 1800tgggaatccg ccccactccg ctccctgtgt ccccaatggc tctgcctaca gtggggacta 1860tatggagcct gagaagccag gcgccccgct tctgccccca cctccccaga acagcgtccc 1920ccattatgcc gaggctgaca ttgttaccct gcagggcgtc accgggggca acacctatcc 1980ccattatgcc gaggctgaca ttgttaccct gcagggcgtc accgggggca acacctatgc 2040tgtgcctgca ctgcccccag gggcagtcgg ggatgggccc cccagagtgg atttccctgc 2100tgtgcctgca ctgcccccag gggcagtcgg ggatgggccc cccagagtgg atttccctcg 2160atctcgactc cgcttcaagg agaagcttgg cgagggccag tttggggagg tgcacctgcg 2220atctcgactc cgcttcaagg agaagcttgg cgagggccag tttggggagg tgcacctgtg 2280tgaggtcgac agccctcaag atctggttag tcttgatttc ccccttaatg tgcgtaagtg 2340tgaggtcgac agccctcaag atctggttag tcttgatttc ccccttaatg tgcgtaaggg 2400acaccctttg ctggtagctg tcaagatctt acggccagat gccaccaaga atgccagggg 2460acaccctttg ctggtagctg tcaagatctt acggccagat gccaccaaga atgccaggaa 2520tgatttcctg aaagaggtga agatcatgtc gaggctcaag gacccaaaca tcattcggaa 2580tgatttcctg aaagaggtga agatcatgtc gaggctcaag gacccaaaca tcattcggct 2640gctgggcgtg tgtgtgcagg acgaccccct ctgcatgatt actgactaca tggagaacct 2700gctgggcgtg tgtgtgcagg acgaccccct ctgcatgatt actgactaca tggagaacgg 2760cgacctcaac cagttcctca gtgcccacca gctggaggac aaggcagccg agggggccgg 2820cgacctcaac cagttcctca gtgcccacca gctggaggac aaggcagccg agggggcccc 2880tggggacggg caggctgcgc aggggcccac catcagctac ccaatgctgc tgcatgtgcc 2940tggggacggg caggctgcgc aggggcccac catcagctac ccaatgctgc tgcatgtggc 3000agcccagatc gcctccggca tgcgctatct ggccacactc aactttgtac atcgggacgc 3060agcccagatc gcctccggca tgcgctatct ggccacactc aactttgtac atcgggacct 3120ggccacgcgg aactgcctag ttggggaaaa tttcaccatc aaaatcgcag actttggcct 3180ggccacgcgg aactgcctag ttggggaaaa tttcaccatc aaaatcgcag actttggcat 3240gagccggaac ctctatgctg gggactatta ccgtgtgcag ggccgggcag tgctgcccat 3300gagccggaac ctctatgctg gggactatta ccgtgtgcag ggccgggcag tgctgcccat 3360ccgctggatg gcctgggagt gcatcctcat ggggaagttc acgactgcga gtgacgtgat 3420ccgctggatg gcctgggagt gcatcctcat ggggaagttc acgactgcga gtgacgtgtg 3480ggcctttggt gtgaccctgt gggaggtgct gatgctctgt agggcccagc cctttgggtg 3540ggcctttggt gtgaccctgt gggaggtgct gatgctctgt agggcccagc cctttgggca 3600gctcaccgac gagcaggtca tcgagaacgc gggggagttc ttccgggacc agggccggca 3660gctcaccgac gagcaggtca tcgagaacgc gggggagttc ttccgggacc agggccggca 3720ggtgtacctg tcccggccgc ctgcctgccc gcagggccta tatgagctga tgcttcggca 3780ggtgtacctg tcccggccgc ctgcctgccc gcagggccta tatgagctga tgcttcggtg 3840ctggagccgg gagtctgagc agcgaccacc cttttcccag ctgcatcggt tcctggcatg 3900ctggagccgg gagtctgagc agcgaccacc cttttcccag ctgcatcggt tcctggcaga 3960ggatgcactc aacacggtgt gaatcacaca tccagctgcc cctccctcag ggagcgatcc 4020aggggaagcc agtgacacta aaacaagagg acacaatggc acctctgccc ttcccctccc 4080gacagcccat cacctctaat agaggcagtg agactgcagg tgggctgggc ccacccaggg 4140agctgatgcc ccttctcccc ttcctggaca cactctcatg tccccttcct gttcttcctt 4200cctagaagcc cctgtcgccc acccagctgg tcctgtggat gggatcctct ccaccctcct 4260ctagccatcc cttggggaag ggtggggaga aatataggat agacactgga catggcccat 4320tggagcacct gggccccact ggacaacact gattcctgga gaggtggctg cgcccccagc 4380ttctctctcc ctgtcacaca ctggacccca ctggctgaga atctgggggt gaggaggaca 4440agaaggagag gaaaatgttt ccttgtgcct gctcctgtac

ttgtcctcag cttgggcttc 4500ttcctcctcc atcacctgaa acactggacc tgggggtagc cccgccccag ccctcagtca 4560cccccacttc ccacttgcag tcttgtagct agaacttctc taagcctata cgtttctgtg 4620gagtaaatat tgggattggg gggaaagagg gagcaacggc ccatagcctt ggggttggac 4680atctctagtg tagctgccac attgattttt ctataatcac ttggggtttg tacatttttg 4740gggggagaga cacagatttt tacactaata tatggaccta gcttgaggca attttaatcc 4800cctgcactag gcaggtaata ataaaggttg agttttcc 483893876PRTHomo Sapiens 93Met Gly Pro Glu Ala Leu Ser Ser Leu Leu Leu Leu Leu Leu Val Ala 1 5 10 15 Ser Gly Asp Ala Asp Met Lys Gly His Phe Asp Pro Ala Lys Cys Arg 20 25 30 Tyr Ala Leu Gly Met Gln Asp Arg Thr Ile Pro Asp Ser Asp Ile Ser 35 40 45 Ala Ser Ser Ser Trp Ser Asp Ser Thr Ala Ala Arg His Ser Arg Leu 50 55 60 Glu Ser Ser Asp Gly Asp Gly Ala Trp Cys Pro Ala Gly Ser Val Phe 65 70 75 80 Pro Lys Glu Glu Glu Tyr Leu Gln Val Asp Leu Gln Arg Leu His Leu 85 90 95 Val Ala Leu Val Gly Thr Gln Gly Arg His Ala Gly Gly Leu Gly Lys 100 105 110 Glu Phe Ser Arg Ser Tyr Arg Leu Arg Tyr Ser Arg Asp Gly Arg Arg 115 120 125 Trp Met Gly Trp Lys Asp Arg Trp Gly Gln Glu Val Ile Ser Gly Asn 130 135 140 Glu Asp Pro Glu Gly Val Val Leu Lys Asp Leu Gly Pro Pro Met Val 145 150 155 160 Ala Arg Leu Val Arg Phe Tyr Pro Arg Ala Asp Arg Val Met Ser Val 165 170 175 Cys Leu Arg Val Glu Leu Tyr Gly Cys Leu Trp Arg Asp Gly Leu Leu 180 185 190 Ser Tyr Thr Ala Pro Val Gly Gln Thr Met Tyr Leu Ser Glu Ala Val 195 200 205 Tyr Leu Asn Asp Ser Thr Tyr Asp Gly His Thr Val Gly Gly Leu Gln 210 215 220 Tyr Gly Gly Leu Gly Gln Leu Ala Asp Gly Val Val Gly Leu Asp Asp 225 230 235 240 Phe Arg Lys Ser Gln Glu Leu Arg Val Trp Pro Gly Tyr Asp Tyr Val 245 250 255 Gly Trp Ser Asn His Ser Phe Ser Ser Gly Tyr Val Glu Met Glu Phe 260 265 270 Glu Phe Asp Arg Leu Arg Ala Phe Gln Ala Met Gln Val His Cys Asn 275 280 285 Asn Met His Thr Leu Gly Ala Arg Leu Pro Gly Gly Val Glu Cys Arg 290 295 300 Phe Arg Arg Gly Pro Ala Met Ala Trp Glu Gly Glu Pro Met Arg His 305 310 315 320 Asn Leu Gly Gly Asn Leu Gly Asp Pro Arg Ala Arg Ala Val Ser Val 325 330 335 Pro Leu Gly Gly Arg Val Ala Arg Phe Leu Gln Cys Arg Phe Leu Phe 340 345 350 Ala Gly Pro Trp Leu Leu Phe Ser Glu Ile Ser Phe Ile Ser Asp Val 355 360 365 Val Asn Asn Ser Ser Pro Ala Leu Gly Gly Thr Phe Pro Pro Ala Pro 370 375 380 Trp Trp Pro Pro Gly Pro Pro Pro Thr Asn Phe Ser Ser Leu Glu Leu 385 390 395 400 Glu Pro Arg Gly Gln Gln Pro Val Ala Lys Ala Glu Gly Ser Pro Thr 405 410 415 Ala Ile Leu Ile Gly Cys Leu Val Ala Ile Ile Leu Leu Leu Leu Leu 420 425 430 Ile Ile Ala Leu Met Leu Trp Arg Leu His Trp Arg Arg Leu Leu Ser 435 440 445 Lys Ala Glu Arg Arg Val Leu Glu Glu Glu Leu Thr Val His Leu Ser 450 455 460 Val Pro Gly Asp Thr Ile Leu Ile Asn Asn Arg Pro Gly Pro Arg Glu 465 470 475 480 Pro Pro Pro Tyr Gln Glu Pro Arg Pro Arg Gly Asn Pro Pro His Ser 485 490 495 Ala Pro Cys Val Pro Asn Gly Ser Ala Tyr Ser Gly Asp Tyr Met Glu 500 505 510 Pro Glu Lys Pro Gly Ala Pro Leu Leu Pro Pro Pro Pro Gln Asn Ser 515 520 525 Val Pro His Tyr Ala Glu Ala Asp Ile Val Thr Leu Gln Gly Val Thr 530 535 540 Gly Gly Asn Thr Tyr Ala Val Pro Ala Leu Pro Pro Gly Ala Val Gly 545 550 555 560 Asp Gly Pro Pro Arg Val Asp Phe Pro Arg Ser Arg Leu Arg Phe Lys 565 570 575 Glu Lys Leu Gly Glu Gly Gln Phe Gly Glu Val His Leu Cys Glu Val 580 585 590 Asp Ser Pro Gln Asp Leu Val Ser Leu Asp Phe Pro Leu Asn Val Arg 595 600 605 Lys Gly His Pro Leu Leu Val Ala Val Lys Ile Leu Arg Pro Asp Ala 610 615 620 Thr Lys Asn Ala Arg Asn Asp Phe Leu Lys Glu Val Lys Ile Met Ser 625 630 635 640 Arg Leu Lys Asp Pro Asn Ile Ile Arg Leu Leu Gly Val Cys Val Gln 645 650 655 Asp Asp Pro Leu Cys Met Ile Thr Asp Tyr Met Glu Asn Gly Asp Leu 660 665 670 Asn Gln Phe Leu Ser Ala His Gln Leu Glu Asp Lys Ala Ala Glu Gly 675 680 685 Ala Pro Gly Asp Gly Gln Ala Ala Gln Gly Pro Thr Ile Ser Tyr Pro 690 695 700 Met Leu Leu His Val Ala Ala Gln Ile Ala Ser Gly Met Arg Tyr Leu 705 710 715 720 Ala Thr Leu Asn Phe Val His Arg Asp Leu Ala Thr Arg Asn Cys Leu 725 730 735 Val Gly Glu Asn Phe Thr Ile Lys Ile Ala Asp Phe Gly Met Ser Arg 740 745 750 Asn Leu Tyr Ala Gly Asp Tyr Tyr Arg Val Gln Gly Arg Ala Val Leu 755 760 765 Pro Ile Arg Trp Met Ala Trp Glu Cys Ile Leu Met Gly Lys Phe Thr 770 775 780 Thr Ala Ser Asp Val Trp Ala Phe Gly Val Thr Leu Trp Glu Val Leu 785 790 795 800 Met Leu Cys Arg Ala Gln Pro Phe Gly Gln Leu Thr Asp Glu Gln Val 805 810 815 Ile Glu Asn Ala Gly Glu Phe Phe Arg Asp Gln Gly Arg Gln Val Tyr 820 825 830 Leu Ser Arg Pro Pro Ala Cys Pro Gln Gly Leu Tyr Glu Leu Met Leu 835 840 845 Arg Cys Trp Ser Arg Glu Ser Glu Gln Arg Pro Pro Phe Ser Gln Leu 850 855 860 His Arg Phe Leu Ala Glu Asp Ala Leu Asn Thr Val 865 870 875 9420DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DDR1 protein" 94catctctgct tccagctcct 209520DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DDR1 protein" 95tactcctcct ccttgggaaa 209619DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DDR1 protein" 96agctaccggc tgcgttact 199720DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DDR1 protein" 97cttcagcacc actccctcag 209819DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DDR1 protein" 98cgtctgtctg cgggtagag 199920DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DDR1 protein" 99ccgtcatagg tggagtcgtt 2010020DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DDR1 protein" 100caacgactcc acctatgacg 2010120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DDR1 protein" 101tgctccatcc cacatagtca 2010220DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DDR1 protein" 102tgactatgtg ggatggagca 2010320DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DDR1 protein" 103ccagcgtgtg catgttgtta 2010418DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DDR1 protein" 104tgtctcagtg ccccttgg 1810519DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DDR1 protein" 105gtgccggaga ggaattgtt 1910619DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DDR1 protein" 106acctcccacc aacttcagc 1910719DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DDR1 protein" 107cagcaggagc aggatgatg 1910819DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DDR1 protein" 108catcatcctg ctcctgctg 1910920DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DDR1 protein" 109ccagggacag agaggtgaac 2011018DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DDR1 protein" 110accgcccagg tcctagag 1811119DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DDR1 protein" 111cggtaggctg gattggaga 1911220DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DDR1 protein" 112caccctttgc tggtagctgt 2011320DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DDR1 protein" 113cgaatgatgt ttgggtcctt 2011420DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 114acagcaggtt ggagagcagt 2011520DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 115gtcaggaggt gatctcaggc 2011620DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 116ctctatggct gcctctggag 2011720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 117gtggggctgg atgactttag 2011820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 118agtttgagtt tgaccggctg 2011920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 119ccctggttac tcttcagcga 2012018DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 120cttggagctg gagcccag 1812120DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 121agggtgttgg aagaggagct 2012219DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 122actctgctcc ctgtgtccc 1912320DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 123gccaggaatg atttcctgaa 2012460DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DDR1 protein" 124attgggattg gggggaaaga gggagcaacg gcccatagcc ttggggttgg acatctctag 601253156DNAHomo Sapiens 125actccgcaac ctgtcgctca ggttcctcct ctcccggccc cgccccggcc cggccccgcc 60gagcgtccca cccgcccgcg ggagacctgg cgccccggcc gaggcgcgaa cagacggacg 120caccggcgag cgccgagggg acaggccgag cgcggggcgc cggaggcagg tgtgggacag 180gcactggcct cagaccgggg ccacactgag gtctgccctt ctcccgctgg ccgccaccca 240agacaccatg agccagtccg gggccgtgag ctgctgcccg ggtgccacca atggcagcct 300gggccggtcc gacggtgtgg ccaagatgag ccccaaggac ctgtttgagc agaggaagaa 360gtattccaac tccaacgtca tcatgcacga gacctcgcag taccacgtcc agcacctggc 420cacattcatc atggacaaga gcgaagccat cacgtctgtg gacgacgcca tccggaagct 480ggtgcagctg agctccaagg agaagatctg gacccaggag atgctgctgc aggtgaacga 540ccagtcgctg cggctgctgg acatcgagtc acaggaggag ctggaagact tcccgctgcc 600cacggtgcag cgcagccaga cggtcctcaa ccagctgcgc tacccgtctg tgctgctgct 660cgtgtgccag gactcggagc agagcaagcc ggatgtccac ttcttccact gcgatgaggt 720ggaggcagag ctggtgcacg aggacatcga gagcgcgttg gccgactgcc ggctgggcaa 780gaagatgcgg ccgcagaccc tgaagggaca ccaggagaag attcggcagc ggcagtccat 840cctgcctcct ccccagggcc cggcgcccat ccccttccag caccgcggcg gggattcccc 900ggaggccaag aatcgcgtgg gcccgcaggt gccactcagc gagccaggtt tccgccgtcg 960ggagtcgcag gaggagccgc gggccgtgct ggctcagaag atagagaagg agacgcaaat 1020cctcaactgc gccctggacg acatcgagtg gtttgtggcc cggctgcaga aggcagccga 1080ggctttcaag cagctgaacc agcggaaaaa ggggaagaag aagggcaaga aggcgccagc 1140agagggcgtc ctcacactgc gggcacggcc cccctctgag ggcgagttca tcgactgctt 1200ccagaaaatc aagctggcga ttaacttgct ggcaaagctg cagaagcaca tccagaaccc 1260cagcgccgcg gagctcgtgc acttcctctt cgggcctctg gacctgatcg tcaacacctg 1320cagtggccca gacatcgcac gctccgtctc ctgcccactg ctctcccgag atgccgtgga 1380cttcctgcgc ggccacctgg tccctaagga gatgtcgctg tgggagtcac tgggagagag 1440ctggatgcgg ccccgttccg agtggccgcg ggagccacag gtgcccctct acgtgcccaa 1500gttccacagc ggctgggagc ctcctgtgga tgtgctgcag gaggccccct gggaggtgga 1560ggggctggcg tctgccccca tcgaggaggt gagtccagtg agccgacagt ccataagaaa 1620ctcccagaag cacagcccca cttcagagcc cacccccccg ggggatgccc taccaccagt 1680cagctcccca catactcaca ggggctacca gccaacacca gccatggcca agtacgtcaa 1740gatcctgtat gacttcacag cccgaaatgc caacgagcta tcggtgctca aggatgaggt 1800cctagaggtg ctggaggacg gccggcagtg gtggaagctg cgcagccgca gcggccaggc 1860ggggtacgtg ccctgcaaca tcctaggcga ggcgcgaccg gaggacgccg gcgccccgtt 1920cgagcaggcc ggtcagaagt actggggccc cgccagcccg acccacaagc tacccccaag 1980cttcccgggg aacaaagacg agctcatgca gcacatggac gaggtcaacg acgagctcat 2040ccggaaaatc agcaacatca gggcgcagcc acagaggcac ttccgcgtgg agcgcagcca 2100gcccgtgagc

cagccgctca cctacgagtc gggtccggac gaggtccgcg cctggctgga 2160agccaaggcc ttcagcccgc ggatcgtgga gaacctgggc atcctgaccg ggccgcagct 2220cttctccctc aacaaggagg agctgaagaa agtgtgcggc gaggagggcg tccgcgtgta 2280cagccagctc accatgcaga aggccttcct ggagaagcag caaagtgggt cggagctgga 2340agaactcatg aacaagtttc attccatgaa tcagaggagg ggggaggaca gctaggccca 2400gctgccttgg gctggggcct gcggagggga agcccaccca caatgcatgg agtattattt 2460ttatatgtgt atgtattttg tatcaaggac acggaggggg tgtggtgctg gctagaggtc 2520cctgcccctg tctggaggca caacgcccat ccttaggcca aacagtaccc aaggcctcag 2580cccacaccaa gactaatctc agccaaacct gctgcttggt ggtgccagcc ccttgtccac 2640cttctcttga ggccacagaa ctccctgggg ctggggcctc tttctctggc ctcccctgtg 2700cacctggggg gtcctggccc ctgtgatgct cccccatccc cacccacttc tacatccatc 2760cacaccccag ggtgagctgg agctccaggc tggccaggct gaacctcgca cacacgcaga 2820gttctgctcc ctgagggggg cccgggaggg gctccagcag gaggccgtgg gtgccattcg 2880ggggaaagtg ggggaacgac acacacttca cctgcaaggg ccgacaacgc aggggacacc 2940gtgccggctt cagacactcc cagcgcccac tcttacaggc ccaggactgg agctttctct 3000ggccaagttt caggccaatg atccccgcat ggtgttgggg gtgctggtgt gtcttggtgc 3060ctggacttga gtctcaccct acagatgaga ggtggctgag gcaccagggc taagcaatta 3120aaccagttaa gtctcccagg aaaaaaaaaa aaaaaa 3156126715PRTHomo Sapiens 126Met Ser Gln Ser Gly Ala Val Ser Cys Cys Pro Gly Ala Thr Asn Gly 1 5 10 15 Ser Leu Gly Arg Ser Asp Gly Val Ala Lys Met Ser Pro Lys Asp Leu 20 25 30 Phe Glu Gln Arg Lys Lys Tyr Ser Asn Ser Asn Val Ile Met His Glu 35 40 45 Thr Ser Gln Tyr His Val Gln His Leu Ala Thr Phe Ile Met Asp Lys 50 55 60 Ser Glu Ala Ile Thr Ser Val Asp Asp Ala Ile Arg Lys Leu Val Gln 65 70 75 80 Leu Ser Ser Lys Glu Lys Ile Trp Thr Gln Glu Met Leu Leu Gln Val 85 90 95 Asn Asp Gln Ser Leu Arg Leu Leu Asp Ile Glu Ser Gln Glu Glu Leu 100 105 110 Glu Asp Phe Pro Leu Pro Thr Val Gln Arg Ser Gln Thr Val Leu Asn 115 120 125 Gln Leu Arg Tyr Pro Ser Val Leu Leu Leu Val Cys Gln Asp Ser Glu 130 135 140 Gln Ser Lys Pro Asp Val His Phe Phe His Cys Asp Glu Val Glu Ala 145 150 155 160 Glu Leu Val His Glu Asp Ile Glu Ser Ala Leu Ala Asp Cys Arg Leu 165 170 175 Gly Lys Lys Met Arg Pro Gln Thr Leu Lys Gly His Gln Glu Lys Ile 180 185 190 Arg Gln Arg Gln Ser Ile Leu Pro Pro Pro Gln Gly Pro Ala Pro Ile 195 200 205 Pro Phe Gln His Arg Gly Gly Asp Ser Pro Glu Ala Lys Asn Arg Val 210 215 220 Gly Pro Gln Val Pro Leu Ser Glu Pro Gly Phe Arg Arg Arg Glu Ser 225 230 235 240 Gln Glu Glu Pro Arg Ala Val Leu Ala Gln Lys Ile Glu Lys Glu Thr 245 250 255 Gln Ile Leu Asn Cys Ala Leu Asp Asp Ile Glu Trp Phe Val Ala Arg 260 265 270 Leu Gln Lys Ala Ala Glu Ala Phe Lys Gln Leu Asn Gln Arg Lys Lys 275 280 285 Gly Lys Lys Lys Gly Lys Lys Ala Pro Ala Glu Gly Val Leu Thr Leu 290 295 300 Arg Ala Arg Pro Pro Ser Glu Gly Glu Phe Ile Asp Cys Phe Gln Lys 305 310 315 320 Ile Lys Leu Ala Ile Asn Leu Leu Ala Lys Leu Gln Lys His Ile Gln 325 330 335 Asn Pro Ser Ala Ala Glu Leu Val His Phe Leu Phe Gly Pro Leu Asp 340 345 350 Leu Ile Val Asn Thr Cys Ser Gly Pro Asp Ile Ala Arg Ser Val Ser 355 360 365 Cys Pro Leu Leu Ser Arg Asp Ala Val Asp Phe Leu Arg Gly His Leu 370 375 380 Val Pro Lys Glu Met Ser Leu Trp Glu Ser Leu Gly Glu Ser Trp Met 385 390 395 400 Arg Pro Arg Ser Glu Trp Pro Arg Glu Pro Gln Val Pro Leu Tyr Val 405 410 415 Pro Lys Phe His Ser Gly Trp Glu Pro Pro Val Asp Val Leu Gln Glu 420 425 430 Ala Pro Trp Glu Val Glu Gly Leu Ala Ser Ala Pro Ile Glu Glu Val 435 440 445 Ser Pro Val Ser Arg Gln Ser Ile Arg Asn Ser Gln Lys His Ser Pro 450 455 460 Thr Ser Glu Pro Thr Pro Pro Gly Asp Ala Leu Pro Pro Val Ser Ser 465 470 475 480 Pro His Thr His Arg Gly Tyr Gln Pro Thr Pro Ala Met Ala Lys Tyr 485 490 495 Val Lys Ile Leu Tyr Asp Phe Thr Ala Arg Asn Ala Asn Glu Leu Ser 500 505 510 Val Leu Lys Asp Glu Val Leu Glu Val Leu Glu Asp Gly Arg Gln Trp 515 520 525 Trp Lys Leu Arg Ser Arg Ser Gly Gln Ala Gly Tyr Val Pro Cys Asn 530 535 540 Ile Leu Gly Glu Ala Arg Pro Glu Asp Ala Gly Ala Pro Phe Glu Gln 545 550 555 560 Ala Gly Gln Lys Tyr Trp Gly Pro Ala Ser Pro Thr His Lys Leu Pro 565 570 575 Pro Ser Phe Pro Gly Asn Lys Asp Glu Leu Met Gln His Met Asp Glu 580 585 590 Val Asn Asp Glu Leu Ile Arg Lys Ile Ser Asn Ile Arg Ala Gln Pro 595 600 605 Gln Arg His Phe Arg Val Glu Arg Ser Gln Pro Val Ser Gln Pro Leu 610 615 620 Thr Tyr Glu Ser Gly Pro Asp Glu Val Arg Ala Trp Leu Glu Ala Lys 625 630 635 640 Ala Phe Ser Pro Arg Ile Val Glu Asn Leu Gly Ile Leu Thr Gly Pro 645 650 655 Gln Leu Phe Ser Leu Asn Lys Glu Glu Leu Lys Lys Val Cys Gly Glu 660 665 670 Glu Gly Val Arg Val Tyr Ser Gln Leu Thr Met Gln Lys Ala Phe Leu 675 680 685 Glu Lys Gln Gln Ser Gly Ser Glu Leu Glu Glu Leu Met Asn Lys Phe 690 695 700 His Ser Met Asn Gln Arg Arg Gly Glu Asp Ser 705 710 715 12718DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 127gagacctggc gccccggc 1812818DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 128gtggccccgg tctgaggc 1812919DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 129gagccagtcc ggggccgtg 1913018DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 130cttggggctc atcttggc 1813121DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 131cgacggtgtg gccaagatga g 2113217DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 132cgtggtactg cgaggtc 1713319DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 133ctccaacgtc atcatgcac 1913419DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 134gatggcgtcg tccacagac 1913519DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 135cagtcgctgc ggctgctgg 1913619DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 136ggaccgtctg gctgcgctg 1913721DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 137gatgtccact tcttccactg c 2113820DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 138ccgaatcttc tcctggtgtc 2013921DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 139gaggccaaga atcgcgtggg c 2114019DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 140gtccagggcg cagttgagg 1914119DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 141cgactgcttc cagaaaatc 1914219DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 142cgaagaggaa gtgcacgag 1914320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 143gatgtcgctg tgggagtcac 2014418DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 144gaggggcacc tgtggctc 1814518DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 145ggtggagggg ctggcgtc 1814620DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EPS8L2 protein" 146ggctctgaag tggggctgtg 2014760DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EPS8L2 protein" 147gcttcccggg gaacaaagac gagctcatgc agcacatgga cgaggtcaac gacgagctca 6014848DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EPS8L2 protein" 148gcagagctgg tgcacgagga catcgagagc gcgttggccg actgccgg 4814951DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EPS8L2 protein" 149gccgtcggga gtcgcaggag gagccgcggg ccgtgctggc tcagaagata g 5115043DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EPS8L2 protein" 150gctcgtgtgc caggactcgg agcagagcaa gccggatgtc cac 4315148DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EPS8L2 protein" 151gtacagccag ctcaccatgc agaaggcctt cctggagaag cagcaaag 481522767DNAHomo Sapiens 152ataaaccctg agatatgagg gttgggcgag acatccgagc ctgtttcgtt ccgtgttggg 60accaggaata accctgactt ctgagctttc ataaccccag gatcctccag aaaatttgcg 120gcgcgctgag ggaaaacctt gctgaagctg tacattggaa tgcgtttaca gtcattgtaa 180tggaagcaaa atacatgaag gaaaaactgt tatttgtatc cctgcttatt gcacctgacg 240actagttgca gatggttttg tttacctaag aaaacttgtg atataaatga aaaaaacacc 300tgttttccta gagtcattgg ttacaaatat gcttcgtcta agagctattt gtccattctc 360ctggagagtg tttcaatttc gacccatcag ttgtgaacca ctaattattc agatgaataa 420gtgtacagat gaggagcaaa tgtttggttt tattgaaaga aacaaagcca tactttcaga 480aaagcaagtg ggatgtgcat ttgatatgct ttggaagctt caaaagcaga agaccagcct 540gttaaaaaat gctgagtatg tcagagacca tcctcaattt cttactcttc ataatttagc 600tacaaataaa ttcaaattaa tgaatgacga taccctggtg aatgtgttat acgtcacaca 660acagtttgct ggtgaggccc atgacccgct agttgaagca ctagttacag aagcatggag 720aaggctagaa aggtttgata ttaaactgct ctcagaattt tcctcttgcc tagcagatca 780gcatttgtat tttagtccat taatgggaaa aatagctgat attgttcata ggaacttgga 840aaccacacag gacttaagtt ccttgtctgt cttgatggtc aacatatctt ctttaatatc 900acgacatttt caacaacaac tggtgaacaa aacagaactt ctttttgaca ccatagattc 960ttctgaggtc aacgttgcaa aaagcatagc aaagtttctt cgaaatgtta gatatcgtta 1020tcaaccacta ttagaaagat gtaataacgt atttttaagt aatgtggacc accttgattt 1080ggattccatc agtaaaatac ttagtgtata caaatttcta caatttaata gttttgaatt 1140tattataatg gctaaaaaga agctaactga aatgattcct ctgtgtaatc atcctgctag 1200ctttgtaaaa ttgtttgtag cattgggacc cattgcagga cctgaagaaa agaaacaact 1260taaatcaact atgttattga tgtcagagga cctaactggc gagcaagccc tggcagtgtt 1320gggagcaatg ggagatatgg aaagcagaaa ctcatgtctg attaaaagag ttacttcagt 1380tctgcataaa catttggatg gctataaacc attagagttg ttgaagataa ctcaagaatt 1440aacttttctg catttccaaa ggaaggagtt ttttgcgaaa cttagagaat tactgcttag 1500ttatttgaaa aatagtttca taccaactga ggtgtctgtt ctggtccgtg ctatttccct 1560gctcccttct cctcacttgg acgaagtggg gatatcccga attgaagccg ttttaccaca 1620gtgtgaccta aataacctga gtagttttgc cacatctgtt ttaagatgga ttcagcatga 1680tcacatgtat ttggataata tgactgcgaa acaactgaaa ctacttcaaa aattagatca 1740ctatggtcgt cagagactac aacacagcaa cagtttggat ctgttacgga aggaacttaa 1800atctctcaaa ggaaacacgt ttcctgagtc acttcttgaa gaaatgattg ctactttaca 1860gcatttcatg gatgatatta attacataaa tgttggggag attgcatctt ttatttctag 1920tactgattac ctcagtactt tgctactaga taggatagcc tcagtggctg ttcagcagat 1980tgaaaagatc catcctttta caatccctgc tattattcgt ccattcagcg tattgaacta 2040tgatccacct caaagggatg aatttttggg aacttgcgtg caacatctta attcttactt 2100aggtatattg gatcctttta tattagtgtt tcttggtttc tctttggcca cacttgaata 2160ttttccagaa gatctgctaa aggcaatttt taacatcaaa ttcttagcta gattggattc 2220tcaacttgaa agtattggtg gcatggatgg aacacaacag cagattttta aaatgttagc 2280agaggtacta ggaggaatca attgtgtaaa agcctcggtt cttacgcctt attaccacaa 2340agtagatttt gagtgtatct tggataaaag aaaaaaacct cttccgtatg gaagccataa 2400tatagcattg ggacaactac cagaaatgcc ctgggaatca aatatcgaaa tagttggatc 2460aaggctgcca ccaggggctg aaaggattgc tttggaattt ttggattcaa aagcactttg 2520tagaaatatc cctcacatga aaggaaaatc tgctatgaaa aaacgacatt tggaaattct 2580ggggtatcgt gtaattcaga tttcccagtt tgaatggaac tctatggcac tgtcaacaaa 2640ggatgctcgg atggactacc tgagagaatg tatatttgga gaagtcaagt catgtttgta 2700gtttttattt aaaatgaatg ttatcgtgtg ttacatttgg acctatttta ataaagtggc 2760ctgtctc 2767153804PRTHomo Sapiens 153Met Lys Lys Thr Pro Val Phe Leu Glu Ser Leu Val Thr Asn Met Leu 1 5 10 15 Arg Leu Arg Ala Ile Cys Pro Phe Ser Trp Arg Val Phe Gln Phe Arg 20 25 30 Pro Ile Ser Cys Glu Pro Leu Ile Ile Gln Met Asn Lys Cys Thr Asp 35 40 45 Glu Glu Gln Met Phe Gly Phe Ile Glu Arg Asn Lys Ala Ile Leu Ser 50 55 60 Glu Lys Gln Val Gly Cys Ala Phe Asp Met Leu Trp Lys Leu Gln Lys 65 70 75 80 Gln Lys Thr Ser Leu Leu Lys Asn Ala Glu Tyr Val Arg Asp His Pro 85 90 95 Gln Phe Leu Thr Leu His Asn Leu Ala Thr Asn Lys Phe Lys Leu Met 100 105 110 Asn Asp Asp Thr Leu Val Asn Val Leu Tyr Val Thr Gln Gln Phe Ala 115 120 125 Gly Glu Ala His Asp Pro Leu Val Glu Ala Leu Val Thr Glu Ala Trp 130 135 140 Arg Arg Leu Glu Arg Phe Asp Ile Lys Leu Leu Ser Glu Phe Ser Ser 145 150 155 160 Cys Leu Ala Asp Gln

His Leu Tyr Phe Ser Pro Leu Met Gly Lys Ile 165 170 175 Ala Asp Ile Val His Arg Asn Leu Glu Thr Thr Gln Asp Leu Ser Ser 180 185 190 Leu Ser Val Leu Met Val Asn Ile Ser Ser Leu Ile Ser Arg His Phe 195 200 205 Gln Gln Gln Leu Val Asn Lys Thr Glu Leu Leu Phe Asp Thr Ile Asp 210 215 220 Ser Ser Glu Val Asn Val Ala Lys Ser Ile Ala Lys Phe Leu Arg Asn 225 230 235 240 Val Arg Tyr Arg Tyr Gln Pro Leu Leu Glu Arg Cys Asn Asn Val Phe 245 250 255 Leu Ser Asn Val Asp His Leu Asp Leu Asp Ser Ile Ser Lys Ile Leu 260 265 270 Ser Val Tyr Lys Phe Leu Gln Phe Asn Ser Phe Glu Phe Ile Ile Met 275 280 285 Ala Lys Lys Lys Leu Thr Glu Met Ile Pro Leu Cys Asn His Pro Ala 290 295 300 Ser Phe Val Lys Leu Phe Val Ala Leu Gly Pro Ile Ala Gly Pro Glu 305 310 315 320 Glu Lys Lys Gln Leu Lys Ser Thr Met Leu Leu Met Ser Glu Asp Leu 325 330 335 Thr Gly Glu Gln Ala Leu Ala Val Leu Gly Ala Met Gly Asp Met Glu 340 345 350 Ser Arg Asn Ser Cys Leu Ile Lys Arg Val Thr Ser Val Leu His Lys 355 360 365 His Leu Asp Gly Tyr Lys Pro Leu Glu Leu Leu Lys Ile Thr Gln Glu 370 375 380 Leu Thr Phe Leu His Phe Gln Arg Lys Glu Phe Phe Ala Lys Leu Arg 385 390 395 400 Glu Leu Leu Leu Ser Tyr Leu Lys Asn Ser Phe Ile Pro Thr Glu Val 405 410 415 Ser Val Leu Val Arg Ala Ile Ser Leu Leu Pro Ser Pro His Leu Asp 420 425 430 Glu Val Gly Ile Ser Arg Ile Glu Ala Val Leu Pro Gln Cys Asp Leu 435 440 445 Asn Asn Leu Ser Ser Phe Ala Thr Ser Val Leu Arg Trp Ile Gln His 450 455 460 Asp His Met Tyr Leu Asp Asn Met Thr Ala Lys Gln Leu Lys Leu Leu 465 470 475 480 Gln Lys Leu Asp His Tyr Gly Arg Gln Arg Leu Gln His Ser Asn Ser 485 490 495 Leu Asp Leu Leu Arg Lys Glu Leu Lys Ser Leu Lys Gly Asn Thr Phe 500 505 510 Pro Glu Ser Leu Leu Glu Glu Met Ile Ala Thr Leu Gln His Phe Met 515 520 525 Asp Asp Ile Asn Tyr Ile Asn Val Gly Glu Ile Ala Ser Phe Ile Ser 530 535 540 Ser Thr Asp Tyr Leu Ser Thr Leu Leu Leu Asp Arg Ile Ala Ser Val 545 550 555 560 Ala Val Gln Gln Ile Glu Lys Ile His Pro Phe Thr Ile Pro Ala Ile 565 570 575 Ile Arg Pro Phe Ser Val Leu Asn Tyr Asp Pro Pro Gln Arg Asp Glu 580 585 590 Phe Leu Gly Thr Cys Val Gln His Leu Asn Ser Tyr Leu Gly Ile Leu 595 600 605 Asp Pro Phe Ile Leu Val Phe Leu Gly Phe Ser Leu Ala Thr Leu Glu 610 615 620 Tyr Phe Pro Glu Asp Leu Leu Lys Ala Ile Phe Asn Ile Lys Phe Leu 625 630 635 640 Ala Arg Leu Asp Ser Gln Leu Glu Ser Ile Gly Gly Met Asp Gly Thr 645 650 655 Gln Gln Gln Ile Phe Lys Met Leu Ala Glu Val Leu Gly Gly Ile Asn 660 665 670 Cys Val Lys Ala Ser Val Leu Thr Pro Tyr Tyr His Lys Val Asp Phe 675 680 685 Glu Cys Ile Leu Asp Lys Arg Lys Lys Pro Leu Pro Tyr Gly Ser His 690 695 700 Asn Ile Ala Leu Gly Gln Leu Pro Glu Met Pro Trp Glu Ser Asn Ile 705 710 715 720 Glu Ile Val Gly Ser Arg Leu Pro Pro Gly Ala Glu Arg Ile Ala Leu 725 730 735 Glu Phe Leu Asp Ser Lys Ala Leu Cys Arg Asn Ile Pro His Met Lys 740 745 750 Gly Lys Ser Ala Met Lys Lys Arg His Leu Glu Ile Leu Gly Tyr Arg 755 760 765 Val Ile Gln Ile Ser Gln Phe Glu Trp Asn Ser Met Ala Leu Ser Thr 770 775 780 Lys Asp Ala Arg Met Asp Tyr Leu Arg Glu Cys Ile Phe Gly Glu Val 785 790 795 800 Lys Ser Cys Leu 15420DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 154tgaatgacga taccctggtg 2015520DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 155agccttctcc atgcttctgt 2015620DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 156ccatgacccg ctagttgaag 2015721DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 157tgatctgcta ggcaagagga a 2115821DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 158ttcctcttgc ctagcagatc a 2115921DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 159tgttgaccat caagacagac a 2116022DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 160tcctctgtgt aatcatcctg ct 2216120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 161ctcgccagtt aggtcctctg 2016220DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 162ggagcaatgg gagatatgga 2016321DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 163ttcctttgga aatgcagaaa a 2116420DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 164tgcatttcca aaggaaggag 2016520DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 165caagtgagga gaagggagca 2016620DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 166aaatgttggg gagattgcat 2016720DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 167tcaatacgct gaatggacga 2016820DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 168gatccacctc aaagggatga 2016920DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 169ggccaaagag aaaccaagaa 2017022DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 170gtgtttcttg gtttctcttt gg 2217120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 171ctgttgtgtt ccatccatgc 2017221DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 172gcattgggac aactaccaga a 2117320DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 173gtatgggagc gcaaaagaag 2017423DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 174tgtgttgctt catatttgta ccc 2317524DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 175catagcagat tttcctttca tgtg 2417620DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 176tgaccgcttc tgtcaacaat 2017721DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding FASTKD1 protein" 177tgaatccaaa aattccaaag c 2117820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 178gacccgctag ttgaagcact 2017920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 179acagaagcat ggagaaggct 2018021DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 180gaacttggaa accacacagg a 2118120DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 181ttgtagcatt gggacccatt 2018220DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 182tgcataaaca tttggatggc 2018320DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 183ttctggtccg tgctatttcc 2018420DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 184gtggctgttc agcagattga 2018520DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 185gaacttgcgt gcaacatctt 2018621DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 186ccagaagatc tgctaaaggc a 2118720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 187tgccctggga atcaaatatc 2018821DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 188ggattgcttt ggaatttttg g 2118920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 189atggatggaa cacaacagca 2019057DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding FASTKD1 protein" 190tgaatggaac tctatggcac tgtcaacaaa ggatgctcgg atggactacc tgagaga 571913263DNAHomo Sapiens 191gagagagctg agagccagga ctcagtgctg agcttggtgt cccaccgcca caaggaggca 60gggaagaaac ccactagtcc cagctcctgg ggtggcacag acattgcaac tggccctgcc 120tgtgggtcct aggggccctt ggctaccagg aggctaagaa cactgctcat gaatgacagt 180gagccctgaa agctctgggg gtgtcaccca gtcccacaag cctgcatccc ctgcagtgga 240gatgggctca gctcctggac gtgccacaga cagaaagcat aacatacact cgccaggaag 300agcctttgcc tgactcaggg cagctcagag tgtggggcag aaggtgacca gccagctcag 360ggcaggagat gcagagcaca gccaattacc tgtggcacac agatgacctg ctggggcagg 420gggccactgc cagtgtgtac aaggcccgca acaagaaatc cggagagctg gttgctgtga 480aggtcttcaa cactaccagc tacctgcggc cccgcgaggt gcaggtgagg gagtttgagg 540tcctgcggaa gctgaaccac cagaacatcg tcaagctctt tgcggtggag gagacgggcg 600gaagccggca gaaggtactg gtgatggagt actgctccag tgggagcctg ctgagtgtgc 660tggagagccc tgagaatgcc tttgggctgc ctgaggatga gttcctggtg gtgctgcgct 720gtgtggtggc cggcatgaac cacctgcggg agaacggcat tgtgcatcgc gacatcaagc 780cggggaacat catgcgcctc gtaggggagg aggggcagag catctacaag ctgacagact 840tcggcgctgc ccgggagctg gatgatgatg agaagttcgt ctcggtctat gggactgagg 900agtacctgca tcccgacatg tatgagcggg cggtgcttcg aaagccccag caaaaagcgt 960tcggggtgac tgtggatctc tggagcattg gagtgacctt gtaccatgca gccactggca 1020gcctgccctt catccccttt ggtgggccac ggcggaacaa ggagatcatg taccggatca 1080ccacggagaa gccggctggg gccattgcag gtgcccagag gcgggagaac gggcccctgg 1140agtggagcta caccctcccc atcacctgcc agctgtcact ggggctgcag agccagctgg 1200tgcccatcct ggccaacatc ctggaggtgg agcaggccaa gtgctggggc ttcgaccagt 1260tctttgcgga gaccagtgac atcctgcagc gagttgtcgt ccatgtcttc tccctgtccc 1320aggcagtcct gcaccacatc tatatccatg cccacaacac gatagccatt ttccaggagg 1380ccgtgcacaa gcagaccagt gtggcccccc gacaccagga gtacctcttt gagggtcacc 1440tctgtgtcct cgagcccagc gtctcagcac agcacatcgc ccacacgacg gcaagcagcc 1500ccctgaccct cttcagcaca gccatcccta aggggctggc cttcagggac cctgctctgg 1560acgtccccaa gttcgtcccc aaagtggacc tgcaggcgga ttacaacact gccaagggcg 1620tgttgggcgc cggctaccag gccctgcggc tggcacgggc cctgctggat gggcaggagc 1680taatgtttcg ggggctgcac tgggtcatgg aggtgctcca ggccacatgc agacggactc 1740tggaagtggc aaggacatcc ctcctctacc tcagcagcag cctgggaact gagaggttca 1800gcagcgtggc tggaacgcct gagatccagg aactgaaggc ggctgcagaa ctgaggtcca 1860ggctgcggac tctagcggag gtcctctcca gatgctccca aaatatcacg gagacccagg 1920agagcctgag cagcctgaac cgggagctgg tgaagagccg ggatcaggta catgaggaca 1980gaagcatcca gcagattcag tgctgtttgg acaagatgaa cttcatctac aaacagttca 2040agaagtctag gatgaggcca gggcttggct acaacgagga gcagattcac aagctggata 2100aggtgaattt cagtcattta gccaaaagac tcctgcaggt gttccaggag gagtgcgtgc 2160agaagtatca agcgtcctta gtcacacacg gcaagaggat gagggtggtg cacgagacca 2220ggaaccacct gcgcctggtt ggctgttctg tggctgcctg taacacagaa gcccaggggg 2280tccaggagag tctcagcaag ctcctggaag agctatctca ccagctcctt caggaccgag 2340caaagggggc tcaggcctcg ccgcctccca tagctcctta ccccagccct acacgaaagg 2400acctgcttct ccacatgcaa gagctctgcg aggggatgaa gctgctggca tctgacctcc 2460tggacaacaa ccgcatcatc gaacggctaa atagagtccc agcacctcct gatgtctgag 2520ctccatgggg cacatgaggc atcctgaagc attagaatga ttccaacact gctcttctgc 2580accatgagac caacccaggg caagatccca tcccatcaca tcagcctacc tccctcctgg 2640ctgctggcca ggatgtcgcc agcattacct tccactgcct ttctccctgg gaagcagcac 2700agctgagact

gggcaccagg ccacctctgt tgggacccac aggaaagagt gtggcagcaa 2760ctgcctggct gacctttcta tcttctctag gctcaggtac tgctcctcca tgcccatggc 2820tgggccgtgg ggagaagaag ctctcatacg ccttcccact ccctctggtt tataggactt 2880cactccctag ccaacaggag aggaggcctc ctggggtttc cccagggcag taggtcaaac 2940gacctcatca cagtcttcct tcctcttcaa gcgtttcatg ttgaacacag ctctctccgc 3000tcccttgtga tttctgaggg tcaccactgc cagcctcagg caacatagag agcctcctgt 3060tctttctatg cttggtctga ctgagcctaa agttgagaaa atgggtggcc aaggccagtg 3120ccagtgtctt ggggcccctt tggctctccc tcactctctg aggctccagc tggtcctggg 3180acatgcagcc aggactgtga gtctgggcag gtccaaggcc tgcaccttca agaagtggaa 3240taaatgtggc ctttgcttct gtt 3263192716PRTHomo Sapiens 192Met Gln Ser Thr Ala Asn Tyr Leu Trp His Thr Asp Asp Leu Leu Gly 1 5 10 15 Gln Gly Ala Thr Ala Ser Val Tyr Lys Ala Arg Asn Lys Lys Ser Gly 20 25 30 Glu Leu Val Ala Val Lys Val Phe Asn Thr Thr Ser Tyr Leu Arg Pro 35 40 45 Arg Glu Val Gln Val Arg Glu Phe Glu Val Leu Arg Lys Leu Asn His 50 55 60 Gln Asn Ile Val Lys Leu Phe Ala Val Glu Glu Thr Gly Gly Ser Arg 65 70 75 80 Gln Lys Val Leu Val Met Glu Tyr Cys Ser Ser Gly Ser Leu Leu Ser 85 90 95 Val Leu Glu Ser Pro Glu Asn Ala Phe Gly Leu Pro Glu Asp Glu Phe 100 105 110 Leu Val Val Leu Arg Cys Val Val Ala Gly Met Asn His Leu Arg Glu 115 120 125 Asn Gly Ile Val His Arg Asp Ile Lys Pro Gly Asn Ile Met Arg Leu 130 135 140 Val Gly Glu Glu Gly Gln Ser Ile Tyr Lys Leu Thr Asp Phe Gly Ala 145 150 155 160 Ala Arg Glu Leu Asp Asp Asp Glu Lys Phe Val Ser Val Tyr Gly Thr 165 170 175 Glu Glu Tyr Leu His Pro Asp Met Tyr Glu Arg Ala Val Leu Arg Lys 180 185 190 Pro Gln Gln Lys Ala Phe Gly Val Thr Val Asp Leu Trp Ser Ile Gly 195 200 205 Val Thr Leu Tyr His Ala Ala Thr Gly Ser Leu Pro Phe Ile Pro Phe 210 215 220 Gly Gly Pro Arg Arg Asn Lys Glu Ile Met Tyr Arg Ile Thr Thr Glu 225 230 235 240 Lys Pro Ala Gly Ala Ile Ala Gly Ala Gln Arg Arg Glu Asn Gly Pro 245 250 255 Leu Glu Trp Ser Tyr Thr Leu Pro Ile Thr Cys Gln Leu Ser Leu Gly 260 265 270 Leu Gln Ser Gln Leu Val Pro Ile Leu Ala Asn Ile Leu Glu Val Glu 275 280 285 Gln Ala Lys Cys Trp Gly Phe Asp Gln Phe Phe Ala Glu Thr Ser Asp 290 295 300 Ile Leu Gln Arg Val Val Val His Val Phe Ser Leu Ser Gln Ala Val 305 310 315 320 Leu His His Ile Tyr Ile His Ala His Asn Thr Ile Ala Ile Phe Gln 325 330 335 Glu Ala Val His Lys Gln Thr Ser Val Ala Pro Arg His Gln Glu Tyr 340 345 350 Leu Phe Glu Gly His Leu Cys Val Leu Glu Pro Ser Val Ser Ala Gln 355 360 365 His Ile Ala His Thr Thr Ala Ser Ser Pro Leu Thr Leu Phe Ser Thr 370 375 380 Ala Ile Pro Lys Gly Leu Ala Phe Arg Asp Pro Ala Leu Asp Val Pro 385 390 395 400 Lys Phe Val Pro Lys Val Asp Leu Gln Ala Asp Tyr Asn Thr Ala Lys 405 410 415 Gly Val Leu Gly Ala Gly Tyr Gln Ala Leu Arg Leu Ala Arg Ala Leu 420 425 430 Leu Asp Gly Gln Glu Leu Met Phe Arg Gly Leu His Trp Val Met Glu 435 440 445 Val Leu Gln Ala Thr Cys Arg Arg Thr Leu Glu Val Ala Arg Thr Ser 450 455 460 Leu Leu Tyr Leu Ser Ser Ser Leu Gly Thr Glu Arg Phe Ser Ser Val 465 470 475 480 Ala Gly Thr Pro Glu Ile Gln Glu Leu Lys Ala Ala Ala Glu Leu Arg 485 490 495 Ser Arg Leu Arg Thr Leu Ala Glu Val Leu Ser Arg Cys Ser Gln Asn 500 505 510 Ile Thr Glu Thr Gln Glu Ser Leu Ser Ser Leu Asn Arg Glu Leu Val 515 520 525 Lys Ser Arg Asp Gln Val His Glu Asp Arg Ser Ile Gln Gln Ile Gln 530 535 540 Cys Cys Leu Asp Lys Met Asn Phe Ile Tyr Lys Gln Phe Lys Lys Ser 545 550 555 560 Arg Met Arg Pro Gly Leu Gly Tyr Asn Glu Glu Gln Ile His Lys Leu 565 570 575 Asp Lys Val Asn Phe Ser His Leu Ala Lys Arg Leu Leu Gln Val Phe 580 585 590 Gln Glu Glu Cys Val Gln Lys Tyr Gln Ala Ser Leu Val Thr His Gly 595 600 605 Lys Arg Met Arg Val Val His Glu Thr Arg Asn His Leu Arg Leu Val 610 615 620 Gly Cys Ser Val Ala Ala Cys Asn Thr Glu Ala Gln Gly Val Gln Glu 625 630 635 640 Ser Leu Ser Lys Leu Leu Glu Glu Leu Ser His Gln Leu Leu Gln Asp 645 650 655 Arg Ala Lys Gly Ala Gln Ala Ser Pro Pro Pro Ile Ala Pro Tyr Pro 660 665 670 Ser Pro Thr Arg Lys Asp Leu Leu Leu His Met Gln Glu Leu Cys Glu 675 680 685 Gly Met Lys Leu Leu Ala Ser Asp Leu Leu Asp Asn Asn Arg Ile Ile 690 695 700 Glu Arg Leu Asn Arg Val Pro Ala Pro Pro Asp Val 705 710 715 19323DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding IKBKE protein" 193gtgccacaga cagaaagcat aac 2319418DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding IKBKE protein" 194ggctgtgctc tgcatctc 1819518DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding IKBKE protein" 195ggggccactg ccagtgtg 1819623DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding IKBKE protein" 196gcaggtagct ggtagtgttg aag 2319721DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding IKBKE protein" 197gaggtcctgc ggaagctgaa c 2119820DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding IKBKE protein" 198cactcagcag gctcccactg 2019921DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding IKBKE protein" 199cctgaggatg agttcctggt g 2120022DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding IKBKE protein" 200gtcgcgatgc acaatgccgt tc 2220124DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding IKBKE protein" 201ggatgatgat gagaagttcg tctc 2420219DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding IKBKE protein" 202gaacgctttt tgctggggc 1920320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding IKBKE protein" 203catccccttt ggtgggccac 2020418DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding IKBKE protein" 204ccgttctccc gcctctgg 1820519DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding IKBKE protein" 205cctggagtgg agctacacc 1920620DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding IKBKE protein" 206cacttggcct gctccacctc 2020719DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding IKBKE protein" 207gtcccaggca gtcctgcac 1920820DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding IKBKE protein" 208gacgctgggc tcgaggacac 2020922DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding IKBKE protein" 209gaccctcttc agcacagcca tc 2221018DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding IKBKE protein" 210gccgcagggc ctggtagc 1821121DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding IKBKE protein" 211gatccaggaa ctgaaggcgg c 2121219DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding IKBKE protein" 212cctgatcccg gctcttcac 1921360DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding IKBKE protein" 213ctcctgttct ttctatgctt ggtctgactg agcctaaagt tgagaaaatg ggtggccaag 6021435DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding IKBKE protein" 214catcacctgc cagctgtcac tggggctgca gagcc 3521535DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding IKBKE protein" 215ctatatccat gcccacaaca cgatagccat tttcc 3521640DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding IKBKE protein" 216ggacgtcccc aagttcgtcc ccaaagtgga cctgcaggcg 4021743DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding IKBKE protein" 217ggtccaggag agtctcagca agctcctgga agagctatct cac 432181578DNAHomo Sapiens 218aaggtgagcg actgcaggca aacccggcga cagcgcagct cgcgtcgacc ctggctcctc 60tgcctgcccc ctcaggcccc cgcctccttc aggatgacgc tggacgtggg gccggaggat 120gagctgcccg actgggccgc cgccaaagag ttttaccaga agtacgaccc taaggacgtc 180atcggcagag gagtgagctc tgtggtccgc cgttgtgttc atcgagctac tggccacgag 240tttgcggtga agattatgga agtgacagct gagcggctga gtcctgagca gctggaggag 300gtgcgggaag ccacacggcg agagacacac atccttcgcc aggtcgccgg ccacccccac 360atcatcaccc tcatcgattc ctacgagtct tctagcttca tgttcctggt gtttgacctg 420atgcggaagg gagagctgtt tgactatctc acagagaagg tggccctctc tgaaaaggaa 480accaggtcca tcatgcggtc tctgctggaa gcagtgagct ttctccatgc caacaacatt 540gtgcatcgag atctgaagcc cgagaatatt ctcctagatg acaatatgca gatccgactt 600tcagatttcg ggttctcctg ccacttggaa cctggcgaga agcttcgaga gttgtgtggg 660accccagggt atctagcgcc agagatcctt aaatgctcca tggatgaaac ccacccaggc 720tatggcaagg aggtcgacct ctgggcctgt ggggtgatct tgttcacact cctggctggc 780tcgccaccct tctggcaccg gcggcagatc ctgatgttac gcatgatcat ggagggccag 840taccagttca gttcccccga gtgggatgac cgttccagca ctgtcaaaga cctgatctcc 900aggctgctgc aggtggatcc tgaggcacgc ctgacagctg agcaggccct acagcacccc 960ttctttgagc gttgtgaagg cagccaaccc tggaacctca ccccccgcca gcggttccgg 1020gtggcagtgt ggacagtgct ggctgctgga cgagtggccc taagcaccca tcgtgtacgg 1080ccactgacca agaatgcact gttgagggac ccttatgcgc tgcggtcagt gcggcacctc 1140atcgacaact gtgccttccg gctctacggg cactgggtaa agaaagggga gcagcagaac 1200cgggcggctc tctttcagca ccggccccct gggccttttc ccatcatggg ccctgaagag 1260gagggagact ctgctgctat aactgaggat gaggccgtgc ttgtgctggg ctaggacctc 1320aaccccaggg attcccagga agcagaactc tccagaagaa gggttttgat cattccagct 1380cctctgggct ctggcctctg gcctcaggcc cactaatgat cctgctaccc tcttgaagac 1440cagcccggta cctctctccc cactggccag gactctgaga tcagagctgg ggtggaaggg 1500agccattctg aacgccacgc ctggcccggt cagtgctgca tgcactgcat atgaaataaa 1560atctgctaca cgccaggg 1578219406PRTHomo Sapiens 219Met Thr Leu Asp Val Gly Pro Glu Asp Glu Leu Pro Asp Trp Ala Ala 1 5 10 15 Ala Lys Glu Phe Tyr Gln Lys Tyr Asp Pro Lys Asp Val Ile Gly Arg 20 25 30 Gly Val Ser Ser Val Val Arg Arg Cys Val His Arg Ala Thr Gly His 35 40 45 Glu Phe Ala Val Lys Ile Met Glu Val Thr Ala Glu Arg Leu Ser Pro 50 55 60 Glu Gln Leu Glu Glu Val Arg Glu Ala Thr Arg Arg Glu Thr His Ile 65 70 75 80 Leu Arg Gln Val Ala Gly His Pro His Ile Ile Thr Leu Ile Asp Ser 85 90 95 Tyr Glu Ser Ser Ser Phe Met Phe Leu Val Phe Asp Leu Met Arg Lys 100 105 110 Gly Glu Leu Phe Asp Tyr Leu Thr Glu Lys Val Ala Leu Ser Glu Lys 115 120 125 Glu Thr Arg Ser Ile Met Arg Ser Leu Leu Glu Ala Val Ser Phe Leu 130 135 140 His Ala Asn Asn Ile Val His Arg Asp Leu Lys Pro Glu Asn Ile Leu 145 150 155 160 Leu Asp Asp Asn Met Gln Ile Arg Leu Ser Asp Phe Gly Phe Ser Cys 165 170 175 His Leu Glu Pro Gly Glu Lys Leu Arg Glu Leu Cys Gly Thr Pro Gly 180 185 190 Tyr Leu Ala Pro Glu Ile Leu Lys Cys Ser Met Asp Glu Thr His Pro 195 200 205 Gly Tyr Gly Lys Glu Val Asp Leu Trp Ala Cys Gly Val Ile Leu Phe 210 215 220 Thr Leu Leu Ala Gly Ser Pro Pro Phe Trp His Arg Arg Gln Ile Leu 225 230 235 240 Met Leu Arg Met Ile Met Glu Gly Gln Tyr Gln Phe Ser Ser Pro Glu 245 250 255 Trp Asp Asp Arg Ser Ser Thr Val Lys Asp Leu Ile Ser Arg Leu Leu 260 265 270 Gln Val Asp Pro Glu Ala Arg Leu Thr Ala Glu Gln Ala Leu Gln His 275 280 285 Pro Phe Phe Glu Arg Cys Glu Gly Ser Gln Pro Trp Asn Leu Thr Pro 290 295 300 Arg Gln Arg Phe Arg Val Ala Val Trp Thr Val Leu Ala Ala Gly Arg 305 310 315 320 Val Ala Leu Ser Thr His Arg Val Arg Pro Leu Thr Lys Asn Ala Leu 325 330 335 Leu Arg Asp Pro Tyr Ala Leu Arg Ser Val Arg His Leu Ile Asp Asn 340 345 350 Cys Ala Phe Arg Leu Tyr Gly His Trp Val Lys Lys Gly Glu Gln Gln 355 360 365 Asn Arg Ala Ala Leu Phe Gln His Arg Pro Pro Gly Pro Phe Pro Ile 370 375 380 Met Gly Pro Glu Glu Glu Gly Asp Ser Ala Ala Ile Thr Glu Asp Glu 385 390 395 400 Ala Val Leu Val Leu Gly 405 22020DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward

primer for amplifying the nucleotide sequence encoding PHKG2 protein" 220ccgccaaaga gttttaccag 2022120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PHKG2 protein" 221tccataatct tcaccgcaaa 2022220DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PHKG2 protein" 222ggcgagagac acacatcctt 2022321DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PHKG2 protein" 223caaacaccag gaacatgaag c 2122421DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PHKG2 protein" 224gcttcatgtt cctggtgttt g 2122520DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PHKG2 protein" 225ttttcagaga gggccacctt 2022621DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PHKG2 protein" 226ggaagggaga gctgtttgac t 2122720DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PHKG2 protein" 227tgttgttggc atggagaaag 2022820DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PHKG2 protein" 228tcagatttcg ggttctcctg 2022920DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PHKG2 protein" 229atagcctggg tgggtttcat 2023020DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PHKG2 protein" 230atgaaaccca cccaggctat 2023120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PHKG2 protein" 231tgcgtaacat caggatctgc 2023220DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PHKG2 protein" 232cgttccagca ctgtcaaaga 2023320DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PHKG2 protein" 233ccttcacaac gctcaaagaa 2023420DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PHKG2 protein" 234accccttctt tgagcgttgt 2023520DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PHKG2 protein" 235cgtacacgat gggtgcttag 2023620DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PHKG2 protein" 236ccgttgtgtt catcgagcta 2023720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PHKG2 protein" 237catcaccctc atcgattcct 2023821DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PHKG2 protein" 238ggaagggaga gctgtttgac t 2123920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PHKG2 protein" 239aggaaaccag gtccatcatg 2024020DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PHKG2 protein" 240cagggtatct agcgccagag 2024120DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PHKG2 protein" 241cctgtggggt gatcttgttc 2024219DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PHKG2 protein" 242acagctgagc aggccctac 1924320DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PHKG2 protein" 243gttgtggcag tgtggacagt 2024460DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PHKG2 protein" 244ctcaacccca gggattccca ggaagcagaa ctctccagaa gaagggtttt gatcattcca 602452578DNAHomo Sapiens 245gagcctcgaa gtccgccggc caatcgaagg cgggccccag cggcgcgtgc gcgccgcggc 60cagcgcgcgc gggcgggggg gcaggcgcgc cccggaccca ggatttataa aggcgaggcc 120gggaccggcg cgcgctctcg tcgcccccgc tgtcccggcg gcgccaaccg aagcgccccg 180cctgatccgt gtccgacatg ctgcgccgcg ctctgctgtg cctggccgtg gccgccctgg 240tgcgcgccga cgcccccgag gaggaggacc acgtcctggt gctgcggaaa agcaacttcg 300cggaggcgct ggcggcccac aagtacctgc tggtggagtt ctatgcccct tggtgtggcc 360actgcaaggc tctggcccct gagtatgcca aagccgctgg gaagctgaag gcagaaggtt 420ccgagatcag gttggccaag gtggacgcca cggaggagtc tgacctggcc cagcagtacg 480gcgtgcgcgg ctatcccacc atcaagttct tcaggaatgg agacacggct tcccccaagg 540aatatacagc tggcagagag gctgatgaca tcgtgaactg gctgaagaag cgcacgggcc 600cggctgccac caccctgcct gacggcgcag ctgcagagtc cttggtggag tccagcgagg 660tggctgtcat cggcttcttc aaggacgtgg agtcggactc tgccaagcag tttttgcagg 720cagcagaggc catcgatgac ataccatttg ggatcacttc caacagtgac gtgttctcca 780aataccagct cgacaaagat ggggttgtcc tctttaagaa gtttgatgaa ggccggaaca 840actttgaagg ggaggtcacc aaggagaacc tgctggactt tatcaaacac aaccagctgc 900cccttgtcat cgagttcacc gagcagacag ccccgaagat ttttggaggt gaaatcaaga 960ctcacatcct gctgttcttg cccaagagtg tgtctgacta tgacggcaaa ctgagcaact 1020tcaaaacagc agccgagagc ttcaagggca agatcctgtt catcttcatc gacagcgacc 1080acaccgacaa ccagcgcatc ctcgagttct ttggcctgaa gaaggaagag tgcccggccg 1140tgcgcctcat caccctggag gaggagatga ccaagtacaa gcccgaatcg gaggagctga 1200cggcagagag gatcacagag ttctgccacc gcttcctgga gggcaaaatc aagccccacc 1260tgatgagcca ggagctgccg gaggactggg acaagcagcc tgtcaaggtg cttgttggga 1320agaactttga agacgtggct tttgatgaga aaaaaaacgt ctttgtggag ttctatgccc 1380catggtgtgg tcactgcaaa cagttggctc ccatttggga taaactggga gagacgtaca 1440aggaccatga gaacatcgtc atcgccaaga tggactcgac tgccaacgag gtggaggccg 1500tcaaagtgca cagcttcccc acactcaagt tctttcctgc cagtgccgac aggacggtca 1560ttgattacaa cggggaacgc acgctggatg gttttaagaa attcctggag agcggtggcc 1620aggatggggc aggggatgat gacgatctcg aggacctgga agaagcagag gagccagaca 1680tggaggaaga cgatgatcag aaagctgtga aagatgaact gtaatacgca aagccagacc 1740cgggcgctgc cgagacccct cgggggctgc acacccagca gcagcgcacg cctccgaagc 1800ctgcggcctc gcttgaagga gggcgtcgcc ggaaacccag ggaacctctc tgaagtgaca 1860cctcacccct acacaccgtc cgttcacccc cgtctcttcc ttctgctttt cggtttttgg 1920aaagggatcc atctccaggc agcccaccct ggtggggctt gtttcctgaa accatgatgt 1980actttttcat acatgagtct gtccagagtg cttgctaccg tgttcggagt ctcgctgcct 2040ccctcccgcg ggaggtttct cctctttttg aaaattccgt ctgtgggatt tttagacatt 2100tttcgacatc agggtatttg ttccaccttg gccaggcctc ctcggagaag cttgtccccc 2160gtgtgggagg gacggagccg gactggacat ggtcactcag taccgcctgc agtgtcgcca 2220tgactgatca tggctcttgc atttttgggt aaatggagac ttccggatcc tgtcagggtg 2280tcccccatgc ctggaagagg agctggtggc tgccagccct ggggcccggc acaggcctgg 2340gccttcccct tccctcaagc cagggctcct cctcctgtcg tgggctcatt gtgaccactg 2400gcctctctac agcacggcct gtggcctgtt caaggcagaa ccacgaccct tgactcccgg 2460gtggggaggt ggccaaggat gctggagctg aatcagacgc tgacagttct tcaggcattt 2520ctatttcaca atcgaattga acacattggc caaataaagt tgaaatttta ccacctgt 2578246508PRTHomo Sapiens 246Met Leu Arg Arg Ala Leu Leu Cys Leu Ala Val Ala Ala Leu Val Arg 1 5 10 15 Ala Asp Ala Pro Glu Glu Glu Asp His Val Leu Val Leu Arg Lys Ser 20 25 30 Asn Phe Ala Glu Ala Leu Ala Ala His Lys Tyr Leu Leu Val Glu Phe 35 40 45 Tyr Ala Pro Trp Cys Gly His Cys Lys Ala Leu Ala Pro Glu Tyr Ala 50 55 60 Lys Ala Ala Gly Lys Leu Lys Ala Glu Gly Ser Glu Ile Arg Leu Ala 65 70 75 80 Lys Val Asp Ala Thr Glu Glu Ser Asp Leu Ala Gln Gln Tyr Gly Val 85 90 95 Arg Gly Tyr Pro Thr Ile Lys Phe Phe Arg Asn Gly Asp Thr Ala Ser 100 105 110 Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala Asp Asp Ile Val Asn Trp 115 120 125 Leu Lys Lys Arg Thr Gly Pro Ala Ala Thr Thr Leu Pro Asp Gly Ala 130 135 140 Ala Ala Glu Ser Leu Val Glu Ser Ser Glu Val Ala Val Ile Gly Phe 145 150 155 160 Phe Lys Asp Val Glu Ser Asp Ser Ala Lys Gln Phe Leu Gln Ala Ala 165 170 175 Glu Ala Ile Asp Asp Ile Pro Phe Gly Ile Thr Ser Asn Ser Asp Val 180 185 190 Phe Ser Lys Tyr Gln Leu Asp Lys Asp Gly Val Val Leu Phe Lys Lys 195 200 205 Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly Glu Val Thr Lys Glu Asn 210 215 220 Leu Leu Asp Phe Ile Lys His Asn Gln Leu Pro Leu Val Ile Glu Phe 225 230 235 240 Thr Glu Gln Thr Ala Pro Lys Ile Phe Gly Gly Glu Ile Lys Thr His 245 250 255 Ile Leu Leu Phe Leu Pro Lys Ser Val Ser Asp Tyr Asp Gly Lys Leu 260 265 270 Ser Asn Phe Lys Thr Ala Ala Glu Ser Phe Lys Gly Lys Ile Leu Phe 275 280 285 Ile Phe Ile Asp Ser Asp His Thr Asp Asn Gln Arg Ile Leu Glu Phe 290 295 300 Phe Gly Leu Lys Lys Glu Glu Cys Pro Ala Val Arg Leu Ile Thr Leu 305 310 315 320 Glu Glu Glu Met Thr Lys Tyr Lys Pro Glu Ser Glu Glu Leu Thr Ala 325 330 335 Glu Arg Ile Thr Glu Phe Cys His Arg Phe Leu Glu Gly Lys Ile Lys 340 345 350 Pro His Leu Met Ser Gln Glu Leu Pro Glu Asp Trp Asp Lys Gln Pro 355 360 365 Val Lys Val Leu Val Gly Lys Asn Phe Glu Asp Val Ala Phe Asp Glu 370 375 380 Lys Lys Asn Val Phe Val Glu Phe Tyr Ala Pro Trp Cys Gly His Cys 385 390 395 400 Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu Gly Glu Thr Tyr Lys Asp 405 410 415 His Glu Asn Ile Val Ile Ala Lys Met Asp Ser Thr Ala Asn Glu Val 420 425 430 Glu Ala Val Lys Val His Ser Phe Pro Thr Leu Lys Phe Phe Pro Ala 435 440 445 Ser Ala Asp Arg Thr Val Ile Asp Tyr Asn Gly Glu Arg Thr Leu Asp 450 455 460 Gly Phe Lys Lys Phe Leu Glu Ser Gly Gly Gln Asp Gly Ala Gly Asp 465 470 475 480 Asp Asp Asp Leu Glu Asp Leu Glu Glu Ala Glu Glu Pro Asp Met Glu 485 490 495 Glu Asp Asp Asp Gln Lys Ala Val Lys Asp Glu Leu 500 505 24719DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P4HB protein" 247gctgcggaaa agcaacttc 1924820DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P4HB protein" 248ctgatctcgg aaccttctgc 2024920DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P4HB protein" 249ggctatccca ccatcaagtt 2025020DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P4HB protein" 250tcttcagcca gttcacgatg 2025120DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P4HB protein" 251gcagagtcct tggtggagtc 2025220DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P4HB protein" 252tggaagtgat cccaaatggt 2025320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P4HB protein" 253accatttggg atcacttcca 2025420DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P4HB protein" 254ggtgacctcc ccttcaaagt 2025520DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P4HB protein" 255ccccttgtca tcgagttcac 2025620DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P4HB protein" 256tgctcagttt gccgtcatag 2025720DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P4HB protein" 257tcacatcctg ctgttcttgc 2025820DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P4HB protein" 258gtcgctgtcg atgaagatga 2025920DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P4HB protein" 259gacggcagag aggatcacag 2026020DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P4HB protein" 260ttcttcccaa caagcacctt 2026120DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P4HB protein" 261agcctgtcaa ggtgcttgtt 2026220DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P4HB protein" 262caaatgggag ccaactgttt 2026320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P4HB protein" 263acagcttccc cacactcaag 2026419DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide

sequence encoding P4HB protein" 264caccgctctc caggaattt 1926520DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P4HB protein" 265gcacgctgga tggttttaag 2026621DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P4HB protein" 266tcatcgtctt cctccatgtc t 2126720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 267cacaagtacc tgctggtgga 2026820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 268ggcttccccc aaggaatata 2026920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 269gcttcttcaa ggacgtggag 2027020DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 270ctcgacaaag atggggttgt 2027120DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 271tcacatcctg ctgttcttgc 2027220DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 272ctatgacggc aaactgagca 2027320DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 273aaaatcaagc cccacctgat 2027420DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 274tgaagacgtg gcttttgatg 2027520DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 275ggtcattgat tacaacgggg 2027620DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 276atgacgatct cgaggacctg 2027760DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P4HB protein" 277ggcatttcta tttcacaatc gaattgaaca cattggccaa ataaagttga aattttcccc 602782026DNAHomo Sapiens 278aagtgctggg atgacaggtg tgagccaccg cccccggccc ctcgcccgcc ttttgaagga 60gcctttcgtc ctcaagggcg aggccactcc ccccccgcga gttccatgcc ccctagaggg 120tcatcgttcc cgacggggag gtggcgccct cccccgggcc ccgggccccg accgcccgtg 180ctgcctcctt ccgggccctc ctccgcgatg acggcgccgc cagcaggcca ggcggactgg 240gcggggctcc gagcggggac tgggacccag accgactagg ggactgggag cgggcggcgc 300ggccatggcg ggctgctgcg ccgcgctggc ggccttcctg ttcgagtacg acacgccgcg 360catcgtgctc atccgcagcc gcaaagtggg gctcatgaac cgcgccgtgc aactgctcat 420cctggcctac gtcatcgggt gggtgtttgt gtgggaaaag ggctaccagg aaactgactc 480cgtggtcagc tccgttacga ccaaggtcaa gggcgtggct gtgaccaaca cttctaaact 540tggattccgg atctgggatg tggcggatta tgtgatacca gctcaggagg aaaactccct 600cttcgtcatg accaacgtga tcctcaccat gaaccagaca cagggcctgt gccccgagat 660tccagatgcg accactgtgt gtaaatcaga tgccagctgt actgccggct ctgccggcac 720ccacagcaac ggagtctcaa caggcaggtg cgtagctttc aacgggtctg tcaagacgtg 780tgaggtggcg gcctggtgcc cggtggagga tgacacacac gtgccacaac ctgctttttt 840aaaggctgca gaaaacttca ctcttttggt taagaacaac atctggtatc ccaaatttaa 900tttcagcaag aggaatatcc ttcccaacat caccactact tacctcaagt cgtgcattta 960tgatgctaaa acagatccct tctgccccat attccgtctt ggcaaaatag tggagaacgc 1020aggacacagt ttccaggaca tggccgtgga gggaggcatc atgggcatcc aggtcaactg 1080ggactgcaac ctggacagag ccgcctccct ctgcttgccc aggtactcct tccgccgcct 1140cgatacacgg gacgttgagc acaacgtatc tcctggctac aatttcaggt ttgccaagta 1200ctacagagac ctggctggca acgagcagcg cacgctcatc aaggcctatg gcatccgctt 1260cgacatcatt gtgtttggga aggcagggaa atttgacatc atccccacta tgatcaacat 1320cggctctggc ctggcactgc taggcatggc gaccgtgctg tgtgacatca tagtcctcta 1380ctgcatgaag aaaagactct actatcggga gaagaaatat aaatatgtgg aagattacga 1440gcagggtctt gctagtgagc tggaccagtg aggcctaccc cacacctggg ctctccacag 1500ccccatcaaa gaacagagag gaggaggagg gagaaatggc caccacatca ccccagagaa 1560atttctggaa tctgattgag tctccactcc acaagcactc agggttcccc agcagctcct 1620gtgtgttgtg tgcaggatct gtttgcccac tcggcccagg aggtcagcag tctgttcttg 1680gctgggtcaa ctctgctttt cccgcaacct ggggttgtcg ggggagcgct ggcccgacgc 1740agtggcactg ctgtggcttt cagggctgga gctggctttg ctcagaagcc tcctgtctcc 1800agctctctcc aggacaggcc cagtcctctg aggcacggcg gctctgttca agcactttat 1860gcggcagggg aggccgcctg gctgcagtca ctagacttgt agcaggcctg ggctgcaggc 1920ttccccccga ccattccctg cagccatgcg gcagagctgg catttctcct cagagaagcg 1980ctgtgctaag gtgatcgagg accagacatt aaagcgtgat tttctt 2026279388PRTHomo Sapiens 279Met Ala Gly Cys Cys Ala Ala Leu Ala Ala Phe Leu Phe Glu Tyr Asp 1 5 10 15 Thr Pro Arg Ile Val Leu Ile Arg Ser Arg Lys Val Gly Leu Met Asn 20 25 30 Arg Ala Val Gln Leu Leu Ile Leu Ala Tyr Val Ile Gly Trp Val Phe 35 40 45 Val Trp Glu Lys Gly Tyr Gln Glu Thr Asp Ser Val Val Ser Ser Val 50 55 60 Thr Thr Lys Val Lys Gly Val Ala Val Thr Asn Thr Ser Lys Leu Gly 65 70 75 80 Phe Arg Ile Trp Asp Val Ala Asp Tyr Val Ile Pro Ala Gln Glu Glu 85 90 95 Asn Ser Leu Phe Val Met Thr Asn Val Ile Leu Thr Met Asn Gln Thr 100 105 110 Gln Gly Leu Cys Pro Glu Ile Pro Asp Ala Thr Thr Val Cys Lys Ser 115 120 125 Asp Ala Ser Cys Thr Ala Gly Ser Ala Gly Thr His Ser Asn Gly Val 130 135 140 Ser Thr Gly Arg Cys Val Ala Phe Asn Gly Ser Val Lys Thr Cys Glu 145 150 155 160 Val Ala Ala Trp Cys Pro Val Glu Asp Asp Thr His Val Pro Gln Pro 165 170 175 Ala Phe Leu Lys Ala Ala Glu Asn Phe Thr Leu Leu Val Lys Asn Asn 180 185 190 Ile Trp Tyr Pro Lys Phe Asn Phe Ser Lys Arg Asn Ile Leu Pro Asn 195 200 205 Ile Thr Thr Thr Tyr Leu Lys Ser Cys Ile Tyr Asp Ala Lys Thr Asp 210 215 220 Pro Phe Cys Pro Ile Phe Arg Leu Gly Lys Ile Val Glu Asn Ala Gly 225 230 235 240 His Ser Phe Gln Asp Met Ala Val Glu Gly Gly Ile Met Gly Ile Gln 245 250 255 Val Asn Trp Asp Cys Asn Leu Asp Arg Ala Ala Ser Leu Cys Leu Pro 260 265 270 Arg Tyr Ser Phe Arg Arg Leu Asp Thr Arg Asp Val Glu His Asn Val 275 280 285 Ser Pro Gly Tyr Asn Phe Arg Phe Ala Lys Tyr Tyr Arg Asp Leu Ala 290 295 300 Gly Asn Glu Gln Arg Thr Leu Ile Lys Ala Tyr Gly Ile Arg Phe Asp 305 310 315 320 Ile Ile Val Phe Gly Lys Ala Gly Lys Phe Asp Ile Ile Pro Thr Met 325 330 335 Ile Asn Ile Gly Ser Gly Leu Ala Leu Leu Gly Met Ala Thr Val Leu 340 345 350 Cys Asp Ile Ile Val Leu Tyr Cys Met Lys Lys Arg Leu Tyr Tyr Arg 355 360 365 Glu Lys Lys Tyr Lys Tyr Val Glu Asp Tyr Glu Gln Gly Leu Ala Ser 370 375 380 Glu Leu Asp Gln 385 280361PRTHomo Sapiens 280Met Ala Gly Cys Cys Ala Ala Leu Ala Ala Phe Leu Phe Glu Tyr Asp 1 5 10 15 Thr Pro Arg Ile Val Leu Ile Arg Ser Arg Lys Val Gly Leu Met Asn 20 25 30 Arg Ala Val Gln Leu Leu Ile Leu Ala Tyr Val Ile Gly Trp Val Phe 35 40 45 Val Trp Glu Lys Gly Tyr Gln Glu Thr Asp Ser Val Val Ser Ser Val 50 55 60 Thr Thr Lys Val Lys Gly Val Ala Val Thr Asn Thr Ser Lys Leu Gly 65 70 75 80 Phe Arg Ile Trp Asp Val Ala Asp Tyr Val Ile Pro Ala Gln Glu Glu 85 90 95 Asn Ser Leu Phe Val Met Thr Asn Val Ile Leu Thr Met Asn Gln Thr 100 105 110 Gln Gly Leu Cys Pro Glu Ile Pro Asp Ala Thr Thr Val Cys Lys Ser 115 120 125 Asp Ala Ser Cys Thr Ala Gly Ser Ala Gly Thr His Ser Asn Val Val 130 135 140 Cys Thr Leu Ile Pro Ala Phe Leu Lys Ala Ala Glu Asn Phe Thr Leu 145 150 155 160 Leu Val Lys Asn Asn Ile Trp Tyr Pro Lys Phe Asn Phe Ser Lys Arg 165 170 175 Asn Ile Leu Pro Asn Ile Thr Thr Thr Tyr Leu Lys Ser Cys Ile Tyr 180 185 190 Asp Ala Lys Thr Asp Pro Phe Cys Pro Ile Phe Arg Leu Gly Lys Ile 195 200 205 Val Glu Asn Ala Gly His Ser Phe Gln Asp Met Ala Val Glu Gly Gly 210 215 220 Ile Met Gly Ile Gln Val Asn Trp Asp Cys Asn Leu Asp Arg Ala Ala 225 230 235 240 Ser Leu Cys Leu Pro Arg Tyr Ser Phe Arg Arg Leu Asp Thr Arg Asp 245 250 255 Val Glu His Asn Val Ser Pro Gly Tyr Asn Phe Arg Phe Ala Lys Tyr 260 265 270 Tyr Arg Asp Leu Ala Gly Asn Glu Gln Arg Thr Leu Ile Lys Ala Tyr 275 280 285 Gly Ile Arg Phe Asp Ile Ile Val Phe Gly Lys Ala Gly Lys Phe Asp 290 295 300 Ile Ile Pro Thr Met Ile Asn Ile Gly Ser Gly Leu Ala Leu Leu Gly 305 310 315 320 Met Ala Thr Val Leu Cys Asp Ile Ile Val Leu Tyr Cys Met Lys Lys 325 330 335 Arg Leu Tyr Tyr Arg Glu Lys Lys Tyr Lys Tyr Val Glu Asp Tyr Glu 340 345 350 Gln Gly Leu Ala Ser Glu Leu Asp Gln 355 360 28120DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P2RX4 protein" 281aactgctcat cctggcctac 2028220DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P2RX4 protein" 282gtcgtaacgg agctgaccac 2028319DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P2RX4 protein" 283ggatgtggcg gattatgtg 1928420DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P2RX4 protein" 284cctgtgtctg gttcatggtg 2028520DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P2RX4 protein" 285agattccaga tgcgaccact 2028620DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P2RX4 protein" 286cagacccgtt gaaagctacg 2028721DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P2RX4 protein" 287tctgtcaaga cgtgtgaggt g 2128822DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P2RX4 protein" 288ccaaaagagt gaagttttct gc 2228923DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P2RX4 protein" 289ttttggttaa gaacaacatc tgg 2329020DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P2RX4 protein" 290atatggggca gaagggatct 2029120DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P2RX4 protein" 291cgcttcgaca tcattgtgtt 2029219DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P2RX4 protein" 292tagcagtgcc aggccagag 1929324DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding P2RX4 protein" 293gaaaagactc tactatcggg agaa 2429420DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding P2RX4 protein" 294ctgttctttg atggggctgt 2029520DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P2RX4 protein" 295ttgtgtggga aaagggctac 2029620DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P2RX4 protein" 296ttcgtcatga ccaacgtgat 2029720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P2RX4 protein" 297tcagatgcca gctgtactgc 2029820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P2RX4 protein" 298gtggaggatg acacacacgt 2029920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P2RX4 protein" 299tccttcccaa catcaccact 2030020DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P2RX4 protein" 300gaaggcaggg aaatttgaca 2030120DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P2RX4 protein" 301gggtcttgct agtgagctgg 2030260DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding P2RX4 protein" 302ctcctcagag aagcgctgtg ctaaggtgat cgaggaccag acattaaagc gtgattttct 6030314PRTArtificial SequenceSource/note="Description of Artificial Sequence Synthetic

peptide representing the C Terminus of the sequence according to NP_002551.2" 303Tyr Arg Glu Lys Lys Tyr Lys Tyr Val Glu Asp Tyr Glu Gln 1 5 10 3043502DNAHomo Sapiens 304gcaggcttct tcggtgcccg agagggagcg ggtgcccaag ggggtggtcc ctgtggcagg 60tcccggggtg ggggcgcggc gctccgggaa gagccttccg caggtccccg ccccgtcacg 120tgggcgccgg ccccggccgc tgcggtcggt ccgctggttg gtcgggcgct tggtccggca 180gttggtcggt gggccagtgg cccgtcgctc gcttctgggc tctcatgttt gaaggtggga 240gggacacggg agcggcccgc acacctgagc cgcccggaga ggagcctcgg ccccgtaccc 300agtaagaaga ggaggaggcc aggcaggcaa aaggagtcat ggcttctgat gctagtcatg 360cgctggaagc tgccctggag caaatggacg ggatcattgc aggcactaaa acaggtgcag 420atcttagtga tggtacttgt gagcctggac tggcttcccc ggcctcctac atgaacccct 480tcccggtgct ccatctcatc gaggacttga ggctggcctt ggagatgctg gagcttcctc 540aggagagagc agccctcctg agccagatcc ctggcccaac agctgcctac ataaaggaat 600ggtttgaaga gagcttgtcc caggtaaacc accacagtgc tgctagtaat gaaacctacc 660aggaacgctt ggcacgtcta gaaggggata aggagtccct catattgcag gtgagtgtcc 720tcacagacca agtagaagcc cagggagaaa agattcgaga cctggaagtg tgtctggaag 780gacaccaggt gaaactcaat gctgctgaag agatgcttca acaggagctg ctaagccgca 840catctcttga gacccagaag ctcgatctga tgactgaagt gtctgagctg aagctcaagc 900tggttggcat ggagaaggag cagagagagc aggaggagaa gcagagaaaa gcagaggagt 960tactgcaaga gctcaggcac ctcaaaatca aagtggaaga gttggaaaat gaaaggaatc 1020agtatgaatg gaagctaaag gccactaagg ctgaagtcgc ccagctgcaa gaacaggtgg 1080ccctgaaaga tgcagaaatt gagcgtctgc acagccagct ctcccggaca gcagctctcc 1140acagtgagag tcacacagag agagaccaag aaattcaacg tctgaaaatg gggatggaaa 1200ctttgctgct tgccaatgaa gataaggacc gtcggataga ggagcttacg gggctgttaa 1260accagtaccg gaaggtaaag gagattgtga tggtcactca agggccttcg gagagaactc 1320tctcaatcaa tgaagaagaa ccggagggag gtttcagcaa gtggaacgct acaaataagg 1380accctgaaga attatttaaa caagagatgc ctccaagatg tagctctcct acagtggggc 1440cacctccatt gccacagaaa tcactggaaa ccagggctca gaaaaagctc tcttgtagtc 1500tagaagactt gagaagtgaa tctgtggata agtgtatgga tgggaaccag cccttcccgg 1560tgttagaacc caaggacagc cctttcttgg cggagcacaa atatcccact ttacctggga 1620agctttcagg agccacgccc aatggagagg ctgccaaatc tcctcccacc atctgccagc 1680ctgacgccac ggggagcagc ctgctgaggc tgagagacac agaaagtggc tgggacgaca 1740ctgctgtggt caatgacctc tcatccacat catcgggcac tgaatcaggt cctcagtctc 1800ctctgacacc agatggtaaa cggaatccca aaggcattaa gaagttctgg ggaaaaatcc 1860gaagaactca gtcaggaaat ttctacactg acacgctggg gatggcagag tttcgacgag 1920gtgggctccg ggcaaccgca gggccaagac tctctaggac cagggactcc aagggacaga 1980aaagtgacgc caatgccccc tttgcccagt ggagcacaga gcgtgtgtgt gcatggctgg 2040aggactttgg cctggctcag tatgtgatct ttgccaggca gtgggtatct tctggccaca 2100ccttattgac agccacccct caggacatgg aaaaggagct aggaattaag cacccactcc 2160acaggaagaa gcttgtttta gcagtgaaag ccatcaacac caaacaggag gagaagtctg 2220cactgctaga ccacatttgg gtgacaaggt ggcttgatga tattggctta ccccagtaca 2280aagaccagtt tcatgaatct agagttgaca gacgaatgct gcaataccta actgtgaacg 2340atttactctt cttaaaagtc accagccaac tacatcatct cagcatcaaa tgtgccattc 2400acgtgctgca tgtcaacaag ttcaaccccc actgcctgca ccggcggcca gctgatgaga 2460gtaacctttc tccttcagaa gttgtacagt ggtccaacca cagggtgatg gagtggttac 2520gatctgtgga cctggcagag tatgcaccca atcttcgagg gagtggagtc catggaggcc 2580tcattatcct ggagccacgc ttcactgggg acaccctggc tatgcttctc aacatccccc 2640cacaaaagac gctcctcagg cgccacctga ccaccaagtt caatgccttg attggtccgg 2700aggctgaaca ggagaagcga gagaaaatgg cctcaccagc ttacacacca ctgaccacca 2760cagccaaagt ccggccaagg aaactaggat tttcacactt cggaaacata agaaaaaaga 2820agttcgatga atcgacggac tacatttgcc caatggagcc cagtgacggt gtcagtgata 2880gtcacagggt ctacagtggc taccggggcc tcagccccct tgatgcccct gaactggatg 2940ggctggacca ggtgggacag attagctgat gcccttgtca cctgccctct gtgcaccctg 3000agagctcaca gtaacactgt gtgtgtcacc atataactgc acctcacccc cgcacgtgtg 3060catgactcgc agagaatatt ccagcaattg tgtacccctg ggccagtctc tttgaaccct 3120gagggtggcc aggatctgga gctgcatctc taaggggcca ggctttgggg accattgcca 3180aaggtggact caggaggaaa gacacttaaa gacactttta catgtctagt aattcttgat 3240gttcatcttc agcaccagtg gaaacacatg aacttcgatg caggtccaga gaccatggac 3300actcccacga ggctcagctc tcaggcaccc cctacacttc agttgaggga aaagctcaag 3360tgccttaggc ccgtggacca cagtcttggc tgagatcaaa gggatgagca acagggactt 3420ctgccacagt gacaatggaa ttgtgttgtg ccttacttca gaggtggtct cttctttctt 3480gtaataaaag caatatttat gc 3502305876PRTHomo Sapiens 305Met Ala Ser Asp Ala Ser His Ala Leu Glu Ala Ala Leu Glu Gln Met 1 5 10 15 Asp Gly Ile Ile Ala Gly Thr Lys Thr Gly Ala Asp Leu Ser Asp Gly 20 25 30 Thr Cys Glu Pro Gly Leu Ala Ser Pro Ala Ser Tyr Met Asn Pro Phe 35 40 45 Pro Val Leu His Leu Ile Glu Asp Leu Arg Leu Ala Leu Glu Met Leu 50 55 60 Glu Leu Pro Gln Glu Arg Ala Ala Leu Leu Ser Gln Ile Pro Gly Pro 65 70 75 80 Thr Ala Ala Tyr Ile Lys Glu Trp Phe Glu Glu Ser Leu Ser Gln Val 85 90 95 Asn His His Ser Ala Ala Ser Asn Glu Thr Tyr Gln Glu Arg Leu Ala 100 105 110 Arg Leu Glu Gly Asp Lys Glu Ser Leu Ile Leu Gln Val Ser Val Leu 115 120 125 Thr Asp Gln Val Glu Ala Gln Gly Glu Lys Ile Arg Asp Leu Glu Val 130 135 140 Cys Leu Glu Gly His Gln Val Lys Leu Asn Ala Ala Glu Glu Met Leu 145 150 155 160 Gln Gln Glu Leu Leu Ser Arg Thr Ser Leu Glu Thr Gln Lys Leu Asp 165 170 175 Leu Met Thr Glu Val Ser Glu Leu Lys Leu Lys Leu Val Gly Met Glu 180 185 190 Lys Glu Gln Arg Glu Gln Glu Glu Lys Gln Arg Lys Ala Glu Glu Leu 195 200 205 Leu Gln Glu Leu Arg His Leu Lys Ile Lys Val Glu Glu Leu Glu Asn 210 215 220 Glu Arg Asn Gln Tyr Glu Trp Lys Leu Lys Ala Thr Lys Ala Glu Val 225 230 235 240 Ala Gln Leu Gln Glu Gln Val Ala Leu Lys Asp Ala Glu Ile Glu Arg 245 250 255 Leu His Ser Gln Leu Ser Arg Thr Ala Ala Leu His Ser Glu Ser His 260 265 270 Thr Glu Arg Asp Gln Glu Ile Gln Arg Leu Lys Met Gly Met Glu Thr 275 280 285 Leu Leu Leu Ala Asn Glu Asp Lys Asp Arg Arg Ile Glu Glu Leu Thr 290 295 300 Gly Leu Leu Asn Gln Tyr Arg Lys Val Lys Glu Ile Val Met Val Thr 305 310 315 320 Gln Gly Pro Ser Glu Arg Thr Leu Ser Ile Asn Glu Glu Glu Pro Glu 325 330 335 Gly Gly Phe Ser Lys Trp Asn Ala Thr Asn Lys Asp Pro Glu Glu Leu 340 345 350 Phe Lys Gln Glu Met Pro Pro Arg Cys Ser Ser Pro Thr Val Gly Pro 355 360 365 Pro Pro Leu Pro Gln Lys Ser Leu Glu Thr Arg Ala Gln Lys Lys Leu 370 375 380 Ser Cys Ser Leu Glu Asp Leu Arg Ser Glu Ser Val Asp Lys Cys Met 385 390 395 400 Asp Gly Asn Gln Pro Phe Pro Val Leu Glu Pro Lys Asp Ser Pro Phe 405 410 415 Leu Ala Glu His Lys Tyr Pro Thr Leu Pro Gly Lys Leu Ser Gly Ala 420 425 430 Thr Pro Asn Gly Glu Ala Ala Lys Ser Pro Pro Thr Ile Cys Gln Pro 435 440 445 Asp Ala Thr Gly Ser Ser Leu Leu Arg Leu Arg Asp Thr Glu Ser Gly 450 455 460 Trp Asp Asp Thr Ala Val Val Asn Asp Leu Ser Ser Thr Ser Ser Gly 465 470 475 480 Thr Glu Ser Gly Pro Gln Ser Pro Leu Thr Pro Asp Gly Lys Arg Asn 485 490 495 Pro Lys Gly Ile Lys Lys Phe Trp Gly Lys Ile Arg Arg Thr Gln Ser 500 505 510 Gly Asn Phe Tyr Thr Asp Thr Leu Gly Met Ala Glu Phe Arg Arg Gly 515 520 525 Gly Leu Arg Ala Thr Ala Gly Pro Arg Leu Ser Arg Thr Arg Asp Ser 530 535 540 Lys Gly Gln Lys Ser Asp Ala Asn Ala Pro Phe Ala Gln Trp Ser Thr 545 550 555 560 Glu Arg Val Cys Ala Trp Leu Glu Asp Phe Gly Leu Ala Gln Tyr Val 565 570 575 Ile Phe Ala Arg Gln Trp Val Ser Ser Gly His Thr Leu Leu Thr Ala 580 585 590 Thr Pro Gln Asp Met Glu Lys Glu Leu Gly Ile Lys His Pro Leu His 595 600 605 Arg Lys Lys Leu Val Leu Ala Val Lys Ala Ile Asn Thr Lys Gln Glu 610 615 620 Glu Lys Ser Ala Leu Leu Asp His Ile Trp Val Thr Arg Trp Leu Asp 625 630 635 640 Asp Ile Gly Leu Pro Gln Tyr Lys Asp Gln Phe His Glu Ser Arg Val 645 650 655 Asp Arg Arg Met Leu Gln Tyr Leu Thr Val Asn Asp Leu Leu Phe Leu 660 665 670 Lys Val Thr Ser Gln Leu His His Leu Ser Ile Lys Cys Ala Ile His 675 680 685 Val Leu His Val Asn Lys Phe Asn Pro His Cys Leu His Arg Arg Pro 690 695 700 Ala Asp Glu Ser Asn Leu Ser Pro Ser Glu Val Val Gln Trp Ser Asn 705 710 715 720 His Arg Val Met Glu Trp Leu Arg Ser Val Asp Leu Ala Glu Tyr Ala 725 730 735 Pro Asn Leu Arg Gly Ser Gly Val His Gly Gly Leu Ile Ile Leu Glu 740 745 750 Pro Arg Phe Thr Gly Asp Thr Leu Ala Met Leu Leu Asn Ile Pro Pro 755 760 765 Gln Lys Thr Leu Leu Arg Arg His Leu Thr Thr Lys Phe Asn Ala Leu 770 775 780 Ile Gly Pro Glu Ala Glu Gln Glu Lys Arg Glu Lys Met Ala Ser Pro 785 790 795 800 Ala Tyr Thr Pro Leu Thr Thr Thr Ala Lys Val Arg Pro Arg Lys Leu 805 810 815 Gly Phe Ser His Phe Gly Asn Ile Arg Lys Lys Lys Phe Asp Glu Ser 820 825 830 Thr Asp Tyr Ile Cys Pro Met Glu Pro Ser Asp Gly Val Ser Asp Ser 835 840 845 His Arg Val Tyr Ser Gly Tyr Arg Gly Leu Ser Pro Leu Asp Ala Pro 850 855 860 Glu Leu Asp Gly Leu Asp Gln Val Gly Gln Ile Ser 865 870 875 30619DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 306gctagtcatg cgctggaag 1930720DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 307gaagctccag catctccaag 2030820DNAArtificial SequenceSource/note="Description of Artificial Sequence forward primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 308cccaggtaaa ccaccacagt 2030920DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 309ctggtgtcct tccagacaca 2031020DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 310tgtgtctgga aggacaccag 2031120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 311tcctcctgct ctctctgctc 2031220DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 312aagagctcag gcacctcaaa 2031320DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 313ctcactgtgg agagctgctg 2031420DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 314aaactttgct gcttgccaat 2031522DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 315ttgagtgacc atcacaatct cc 2231624DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 316tctctcaatc aatgaagaag aacc 2431721DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 317tccagtgatt tctgtggcaa t 2131821DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 318gcctccaaga tgtagctctc c 2131923DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 319tccacagatt cacttctcaa gtc 2332020DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 320cggagcacaa atatcccact 2032120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 321ctttgggatt ccgtttacca 2032220DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 322tggtaaacgg aatcccaaag 2032320DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 323ttggagtccc tggtcctaga 2032420DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 324tctaggacca gggactccaa 2032520DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPFIBP2 protein" 325gggtggctgt caataaggtg 2032620DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 326caggcactaa aacaggtgca 2032720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 327aggggataag gagtccctca 2032820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 328ttgagaccca gaagctcgat 2032920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 329gaaattgagc gtctgcacag 2033020DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 330ttacggggct gttaaaccag 2033120DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 331cagcaagtgg aacgctacaa

2033220DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 332tgccacagaa atcactggaa 2033320DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 333acacagaaag tggctgggac 2033420DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 334ttctacactg acacgctggg 2033520DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 335ggcctggctc agtatgtgat 2033660DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPFIBP2 protein" 336agatcaaagg gatgagcaac agggacttct gccacagtga caatggaatt gtgttgtgcc 603372326DNAHomo Sapiens 337gtgaaaagag gactctcagg ggctcacagg ggctctcact gctggttggc cctgccctcc 60cttccccctc agcagggtgc ccggaagctg gaaccttgtt atctgggtaa ttagtttcag 120accctgcact gaggccggcc aggtctcggg gctgcctccc ataggttgtg caccctgacc 180ccgagaggga ggcgaggcgc tgcttgtcga cagctagagg ctggcctggg gagcaggttt 240ggggtgccct cccacactgc cctccctgcc ccggcccatg ccccccaggg ctgcctgggc 300ctggttattg tgtggggcct cctgacccag ccaagggcac gaagctctgg gaaggggatg 360cccccgaggg tgccagtcca gctagctgcc ccacccctca ggcccagcct ggcccccaag 420ctccccactc tggtgccccg agcagccctg tgggcaagca gccgccgcca tggccgagca 480cctggagctg ctggcagaga tgcccatggt gggcaggatg agcacacagg agcggctgaa 540gcatgcccag aagcggcgcg cccagcaggt gaagatgtgg gcccaggctg agaaggaggc 600ccagggcaag aagggtcctg gggagcgtcc ccggaaggag gcagccagcc aagggctcct 660gaagcaggtc ctcttccctc ccagtgttgt ccttctggag gccgctgccc gaaatgacct 720ggaagaagtc cgccagttcc ttgggagtgg ggtcagccct gacttggcca acgaggacgg 780cctgacggcc ctgcaccagt gctgcattga tgatttccga gagatggtgc agcagctcct 840ggaggctggg gccaacatca atgcctgtga cagtgagtgc tggacgcctc tgcatgctgc 900ggccacctgc ggccacctgc acctggtgga gctgctcatc gccagtggcg ccaatctcct 960ggcggtcaac accgacggga acatgcccta tgacctgtgt gatgatgagc agacgctgga 1020ctgcctggag actgccatgg ccgaccgtgg catcacccag gacagcatcg aggccgcccg 1080ggccgtgcca gaactgcgca tgctggacga catccggagc cggctgcagg ccggggcaga 1140cctccatgcc cccctggacc acggggccac gctgctgcac gtcgcagccg ccaacgggtt 1200cagcgaggcg gctgccctgc tgctggaaca ccgagccagc ctgagcgcta aggaccaaga 1260cggctgggag ccgctgcacg ccgcggccta ctggggccag gtgcccctgg tggagctgct 1320cgtggcgcac ggggccgacc tgaacgcaaa gtccctgatg gacgagacgc cccttgatgt 1380gtgcggggac gaggaggtgc gggccaagct gctggagctg aagcacaagc acgacgccct 1440cctgcgcgcc cagagccgcc agcgctcctt gctgcgccgc cgcacctcca gcgccggcag 1500ccgcgggaag gtggtgaggc gggtgagcct aacccagcgc accgacctgt accgcaagca 1560gcacgcccag gaggccatcg tgtggcaaca gccgccgccc accagcccgg agccgcccga 1620ggacaacgat gaccgccaga caggcgcaga gctcaggccg ccgcccccgg aggaggacaa 1680ccccgaagtg gtcaggccgc acaatggccg agtagggggc tccccagtgc ggcatctata 1740ctccaagcga ctagaccgga gtgtctccta ccagctgagc cccctggaca gcaccacccc 1800ccacaccctg gtccacgaca aggcccacca caccctggct gacctgaagc gccagcgagc 1860tgctgccaag ctgcagcgac ccccacctga ggggcccgag agccctgaga cagctgagcc 1920tggcctgcct ggtgacacgg tgacccccca gcctgactgt ggcttcaggg caggcgggga 1980cccacccctg ctcaagctca cagccccggc ggtggaggct cccgtggaga ggaggccgtg 2040ctgcctgctc atgtgaggct gttgctcagc atgcaggggc cctgtcgcgg gcacagccca 2100aggctgcctc cccacggtgc gtgccctggt gctgcgggtg cagcacggaa accccggctt 2160ctactgtaca ggacactggc ccctctcagg tcagaagaca tgcctggagg gatgtctggc 2220tgcaaagact atttttatcc tgcaactctt gataaagggc tgttttgcca tggaaaaaaa 2280aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 2326338528PRTHomo Sapiens 338Met Ala Glu His Leu Glu Leu Leu Ala Glu Met Pro Met Val Gly Arg 1 5 10 15 Met Ser Thr Gln Glu Arg Leu Lys His Ala Gln Lys Arg Arg Ala Gln 20 25 30 Gln Val Lys Met Trp Ala Gln Ala Glu Lys Glu Ala Gln Gly Lys Lys 35 40 45 Gly Pro Gly Glu Arg Pro Arg Lys Glu Ala Ala Ser Gln Gly Leu Leu 50 55 60 Lys Gln Val Leu Phe Pro Pro Ser Val Val Leu Leu Glu Ala Ala Ala 65 70 75 80 Arg Asn Asp Leu Glu Glu Val Arg Gln Phe Leu Gly Ser Gly Val Ser 85 90 95 Pro Asp Leu Ala Asn Glu Asp Gly Leu Thr Ala Leu His Gln Cys Cys 100 105 110 Ile Asp Asp Phe Arg Glu Met Val Gln Gln Leu Leu Glu Ala Gly Ala 115 120 125 Asn Ile Asn Ala Cys Asp Ser Glu Cys Trp Thr Pro Leu His Ala Ala 130 135 140 Ala Thr Cys Gly His Leu His Leu Val Glu Leu Leu Ile Ala Ser Gly 145 150 155 160 Ala Asn Leu Leu Ala Val Asn Thr Asp Gly Asn Met Pro Tyr Asp Leu 165 170 175 Cys Asp Asp Glu Gln Thr Leu Asp Cys Leu Glu Thr Ala Met Ala Asp 180 185 190 Arg Gly Ile Thr Gln Asp Ser Ile Glu Ala Ala Arg Ala Val Pro Glu 195 200 205 Leu Arg Met Leu Asp Asp Ile Arg Ser Arg Leu Gln Ala Gly Ala Asp 210 215 220 Leu His Ala Pro Leu Asp His Gly Ala Thr Leu Leu His Val Ala Ala 225 230 235 240 Ala Asn Gly Phe Ser Glu Ala Ala Ala Leu Leu Leu Glu His Arg Ala 245 250 255 Ser Leu Ser Ala Lys Asp Gln Asp Gly Trp Glu Pro Leu His Ala Ala 260 265 270 Ala Tyr Trp Gly Gln Val Pro Leu Val Glu Leu Leu Val Ala His Gly 275 280 285 Ala Asp Leu Asn Ala Lys Ser Leu Met Asp Glu Thr Pro Leu Asp Val 290 295 300 Cys Gly Asp Glu Glu Val Arg Ala Lys Leu Leu Glu Leu Lys His Lys 305 310 315 320 His Asp Ala Leu Leu Arg Ala Gln Ser Arg Gln Arg Ser Leu Leu Arg 325 330 335 Arg Arg Thr Ser Ser Ala Gly Ser Arg Gly Lys Val Val Arg Arg Val 340 345 350 Ser Leu Thr Gln Arg Thr Asp Leu Tyr Arg Lys Gln His Ala Gln Glu 355 360 365 Ala Ile Val Trp Gln Gln Pro Pro Pro Thr Ser Pro Glu Pro Pro Glu 370 375 380 Asp Asn Asp Asp Arg Gln Thr Gly Ala Glu Leu Arg Pro Pro Pro Pro 385 390 395 400 Glu Glu Asp Asn Pro Glu Val Val Arg Pro His Asn Gly Arg Val Gly 405 410 415 Gly Ser Pro Val Arg His Leu Tyr Ser Lys Arg Leu Asp Arg Ser Val 420 425 430 Ser Tyr Gln Leu Ser Pro Leu Asp Ser Thr Thr Pro His Thr Leu Val 435 440 445 His Asp Lys Ala His His Thr Leu Ala Asp Leu Lys Arg Gln Arg Ala 450 455 460 Ala Ala Lys Leu Gln Arg Pro Pro Pro Glu Gly Pro Glu Ser Pro Glu 465 470 475 480 Thr Ala Glu Pro Gly Leu Pro Gly Asp Thr Val Thr Pro Gln Pro Asp 485 490 495 Cys Gly Phe Arg Ala Gly Gly Asp Pro Pro Leu Leu Lys Leu Thr Ala 500 505 510 Pro Ala Val Glu Ala Pro Val Glu Arg Arg Pro Cys Cys Leu Leu Met 515 520 525 33921DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 339gtgttgtcct tctggaggcc g 2134021DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 340gccgtcaggc cgtcctcgtt g 2134119DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 341gctgcccgaa atgacctgg 1934219DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 342cggaaatcat caatgcagc 1934320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 343gacgcctctg catgctgcgg 2034421DNAArtificial SequenceSourceR/note="Description of Artificial Sequence everse primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 344cacaggtcat agggcatgtt c 2134520DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 345gatgagcaga cgctggactg 2034618DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 346ctccggatgt cgtccagc 1834718DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 347caggccgggg cagacctc 1834821DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 348ggctcggtgt tccagcagca g 2134917DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 349gggagccgct gcacgcc 1735018DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 350cccgcacctc ctcgtccc 1835118DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 351ctgcgcgccc agagccgc 1835218DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 352gcgtgctgct tgcggtac 1835320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 353gccagacagg cgcagagctc 2035418DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding PPP1R16A protein" 354ctactcggcc attgtgcg 1835581DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPP1R16A protein" 355tctactgtac aggacactgg cccctctcag gtcagaagac atgcctggag ggatgtctgg 60ctgcaaagac tatttttatc c 8135637DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPP1R16A protein" 356ctgacggccc tgcaccagtg ctgcattgat gatttcc 3735731DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPP1R16A protein" 357gactgccatg gccgaccgtg gcatcaccca g 3135830DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPP1R16A protein" 358gctcgtggcg cacggggccg acctgaacgc 3035929DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding PPP1R16A protein" 359gcgccggcag ccgcgggaag gtggtgagg 293601539DNAHomo Sapiens 360gaattcgggg ggagggggca gtgtcctccg agccaggaca ggcatgttgt tgggactggc 60ggccatggag ctgaaggtgt gggtggatgg catccagcgt gtggtctgtg gggtctcaga 120gcagaccacc tgccaggaag tggtcatcgc actagcccaa gcaataggcc agactggccg 180ctttgtgctt gtgcagcggc ttcgggagaa ggagcggcag ttgctgccac aagagtgtcc 240agtgggcgcc caggccacct gcggacagtt tgccagcgat gtccagtttg tcctgaggcg 300cacagggccc agcctagctg ggaggccctc ctcagacagc tgtccacccc cggaacgctg 360cctaattcgt gccagcctcc ctgtaaagcc acgggctgcg ctgggctgtg agccccgcaa 420aacactgacc cccgagccag cccccagcct ctcacgccct gggcctgcgg cccctgtgac 480acccacacca ggctgctgca cagacctgcg gggcctggag ctcagggtgc agaggaatgc 540tgaggagctg ggccatgagg ccttctggga gcaagagctg cgccgggagc aggcccggga 600gcgagaggga caggcacgcc tgcaggcact aagtgcggcc actgctgagc atgccgcccg 660gctgcaggcc ctggacgctc aggcccgtgc cctggaggct gagctgcagc tggcagcgga 720ggcccctggg cccccctcac ctatggcatc tgccactgag cgcctgcacc aggacctggc 780tgttcaggag cggcagagtg cggaggtgca gggcagcctg gctctggtga gccgggccct 840ggaggcagca gagcgagcct tgcaggctca ggctcaggag ctggaggagc tgaaccgaga 900gctccgtcag tgcaacctgc agcagttcat ccagcagacc ggggctgcgc tgccaccgcc 960cccacggcct gacaggggcc ctcctggcac tcagggccct ctgcctccag ccagagagga 1020gtccctcctg ggcgctccct ctgagtccca tgctggtgcc cagcctaggc cccgaggtgg 1080cccccatgac gcagaactcc tggaggtagc agcagctcct gccccagagt ggtgtcctct 1140ggcagcccag ccccaggctc tgtgacagcc tagtgagggc tgcaagacca tcctgcccgg 1200accacagaag gagagttggc ggtcacagag ggctcctctg ccaggcagtg ggaagccctg 1260ggtttggcct caggagctgg gggtgcagtg ggggactgcc ctagtccttg ccaggtcgcc 1320cagcaccctg gagaagcatg gggcgtagcc agctcggaac ttgccaggcc ccaaaggcca 1380cgactgcctg ttggggacag gagatgcatg gacagtgtgc tcaagctgtg ggcatgtgct 1440tgcctgcggg agaggtcctt cactgtgtgt acacagcaag agcatgtgtg tgccacttcc 1500cctaccccaa cgtgaaaacc tcaataaact gcccgaagc 1539361373PRTHomo Sapiens 361Met Leu Leu Gly Leu Ala Ala Met Glu Leu Lys Val Trp Val Asp Gly 1 5 10 15 Ile Gln Arg Val Val Cys Gly Val Ser Glu Gln Thr Thr Cys Gln Glu 20 25 30 Val Val Ile Ala Leu Ala Gln Ala Ile Gly Gln Thr Gly Arg Phe Val 35 40 45 Leu Val Gln Arg Leu Arg Glu Lys Glu Arg Gln Leu Leu Pro Gln Glu 50 55 60 Cys Pro Val Gly Ala Gln Ala Thr Cys Gly Gln Phe Ala Ser Asp Val 65 70 75 80 Gln Phe Val Leu Arg Arg Thr Gly Pro Ser Leu Ala Gly Arg Pro Ser 85 90 95 Ser Asp Ser Cys Pro Pro Pro Glu Arg Cys Leu Ile Arg Ala Ser Leu 100 105 110 Pro Val Lys Pro Arg Ala Ala Leu Gly Cys Glu Pro Arg Lys Thr Leu 115 120 125 Thr Pro Glu Pro Ala Pro Ser Leu Ser Arg Pro Gly Pro Ala Ala Pro 130 135 140 Val Thr Pro Thr Pro Gly Cys Cys Thr Asp Leu Arg Gly Leu Glu Leu 145 150 155 160 Arg Val Gln Arg Asn Ala Glu Glu Leu Gly His Glu Ala Phe Trp Glu 165 170 175 Gln Glu Leu Arg Arg Glu Gln Ala Arg Glu Arg Glu Gly Gln Ala Arg 180 185 190 Leu Gln Ala Leu Ser Ala Ala Thr Ala Glu His Ala Ala Arg Leu Gln 195 200 205 Ala Leu Asp Ala Gln Ala Arg Ala Leu Glu Ala Glu Leu Gln Leu Ala 210 215 220 Ala Glu Ala Pro Gly Pro Pro Ser Pro Met Ala Ser Ala Thr Glu Arg 225 230 235 240 Leu His Gln Asp Leu Ala Val Gln Glu Arg Gln Ser Ala Glu Val Gln 245 250 255 Gly Ser Leu Ala Leu Val Ser Arg Ala Leu Glu Ala Ala Glu Arg Ala 260 265 270 Leu

Gln Ala Gln Ala Gln Glu Leu Glu Glu Leu Asn Arg Glu Leu Arg 275 280 285 Gln Cys Asn Leu Gln Gln Phe Ile Gln Gln Thr Gly Ala Ala Leu Pro 290 295 300 Pro Pro Pro Arg Pro Asp Arg Gly Pro Pro Gly Thr Gln Gly Pro Leu 305 310 315 320 Pro Pro Ala Arg Glu Glu Ser Leu Leu Gly Ala Pro Ser Glu Ser His 325 330 335 Ala Gly Ala Gln Pro Arg Pro Arg Gly Gly Pro His Asp Ala Glu Leu 340 345 350 Leu Glu Val Ala Ala Ala Pro Ala Pro Glu Trp Cys Pro Leu Ala Ala 355 360 365 Gln Pro Gln Ala Leu 370 36219DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RASSF7 protein" 362ctgccaggaa gtggtcatc 1936317DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RASSF7 protein" 363gccgctgcac aagcaca 1736416DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RASSF7 protein" 364catggagctg aaggtg 1636517DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RASSF7 protein" 365ctcaggacaa actggac 1736616DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RASSF7 protein" 366gccactgagc gcctgc 1636717DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RASSF7 protein" 367gtctgctgga tgaactg 1736820DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RASSF7 protein" 368cagcagagcg agccttgcag 2036917DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RASSF7 protein" 369ctgagtgcca ggagggc 1737018DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RASSF7 protein" 370cacggcctga caggggcc 1837115DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RASSF7 protein" 371gcctaggctg ggcac 1537218DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RASSF7 protein" 372ctctgagtcc catgctgg 1837316DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RASSF7 protein" 373gacaccactc tggggc 1637416DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RASSF7 protein" 374tgcccagcct aggccc 1637517DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RASSF7 protein" 375gccagaggac accactc 1737650DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RASSF7 protein" 376gagaggtcct tcactgtgtg tacacagcaa gagcatgtgt gtgccacttc 5037751DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RASSF7 protein" 377agtgtcctcc gagccaggac aggcatgttg ttgggactgg cggccatgga g 5137855DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RASSF7 protein" 378gagccgggcc ctggaggcag cagagcgagc cttgcaggct caggctcagg agctg 5537957DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RASSF7 protein" 379cggcctgaca ggggccctcc tggcactcag ggccctctgc ctccagccag agaggag 5738060DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RASSF7 protein" 380gaggagctgg gccatgaggc cttctgggag caagagctgc gccgggagca ggcccgggag 6038114PRTArtificial SequenceSource/note="Description of Artificial Sequence Epitope of RASSF7" 381Cys Thr Asp Leu Arg Gly Leu Glu Leu Arg Val Gln Arg Asn 1 5 10 3821237DNAHomo Sapiens 382cgattcaggg gagggagcaa ctggagcctc aggccctcca gagtagtctg cctgaccacc 60ctggagccca cagaagccca ggacgtctcc cgcgaagcct ccccgtgtgt ggctgaggat 120ggctgagcag cagggccggg agcttgaggc tgagtgcccc gtctgctgga accccttcaa 180caacacgttc cataccccca aaatgctgga ttgctgccac tccttctgcg tggaatgtct 240ggcccacctc agccttgtga ctccagcccg gcgccgcctg ctgtgcccac tctgtcgcca 300gcccacagtg ctggcctcag ggcagcctgt cactgacttg cccacggaca ctgccatgct 360cgccctgctc cgcctggagc cccaccatgt catcctggaa ggccatcagc tgtgcctcaa 420ggaccagccc aagagccgct acttcctgcg ccagcctcaa gtctacacgc tggaccttgg 480cccccagcct gggggccaga ctgggccgcc cccagacacg gcctctgcca ccgtgtctac 540gcccatcctc atccccagcc accactcttt gagggagtgt ttccgcaacc ctcagttccg 600catctttgcc tacctgatgg ccgtcatcct cagtgtcact ctgttgctca tattctccat 660cttttggacc aagcagttcc tttggggtgt ggggtgagtg ctgttcccag acaagaaacc 720aaaccttttt cggttgctgc tgggtatggt gactacggag cctcatttgg tattgtcttc 780ctttgtagtg ttgtttattt tacaatccag ggattgttca ggccatgtgt ttgcttctgg 840gaacaatttt aaaaaaaaac aaaaaaacga aaagcttgaa ggactgggag atgtggagcg 900acctccgggt gtgagtgtgg cgtcatggaa gggcagagaa gcggttctga ccacagagct 960ccacagcaag ttgtgccaaa gggctgcaca gtggtatcca ggaacctgac tagcccaaat 1020agcaagttgc atttctcact ggagctgctt caaaatcagt gcatattttt ttgagttgct 1080cttttactat gggttgctaa aaaaaaaaaa aaaattggga agtgagcttc aattctgtgg 1140gtaaatgtgt gtttgtttct ctttgaatgt cttgccactg gttgcagtaa aagtgttctg 1200tattcattaa aaaaaaaaaa aaaaaaaaaa aaaaaaa 1237383192PRTHomo Sapiens 383Met Ala Glu Gln Gln Gly Arg Glu Leu Glu Ala Glu Cys Pro Val Cys 1 5 10 15 Trp Asn Pro Phe Asn Asn Thr Phe His Thr Pro Lys Met Leu Asp Cys 20 25 30 Cys His Ser Phe Cys Val Glu Cys Leu Ala His Leu Ser Leu Val Thr 35 40 45 Pro Ala Arg Arg Arg Leu Leu Cys Pro Leu Cys Arg Gln Pro Thr Val 50 55 60 Leu Ala Ser Gly Gln Pro Val Thr Asp Leu Pro Thr Asp Thr Ala Met 65 70 75 80 Leu Ala Leu Leu Arg Leu Glu Pro His His Val Ile Leu Glu Gly His 85 90 95 Gln Leu Cys Leu Lys Asp Gln Pro Lys Ser Arg Tyr Phe Leu Arg Gln 100 105 110 Pro Gln Val Tyr Thr Leu Asp Leu Gly Pro Gln Pro Gly Gly Gln Thr 115 120 125 Gly Pro Pro Pro Asp Thr Ala Ser Ala Thr Val Ser Thr Pro Ile Leu 130 135 140 Ile Pro Ser His His Ser Leu Arg Glu Cys Phe Arg Asn Pro Gln Phe 145 150 155 160 Arg Ile Phe Ala Tyr Leu Met Ala Val Ile Leu Ser Val Thr Leu Leu 165 170 175 Leu Ile Phe Ser Ile Phe Trp Thr Lys Gln Phe Leu Trp Gly Val Gly 180 185 190 38417DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RNF183 protein" 384gagaagctgg gctggag 1738516DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RNF183 protein" 385cagccacaca cgggga 1638622DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RNF183 protein" 386cagctgtgtg ctaagaacaa ag 2238719DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RNF183 protein" 387gccctgctgc tcagccatc 1938818DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RNF183 protein" 388gcagaaggca gcgaggac 1838920DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RNF183 protein" 389ggcagcaatc cagcattttg 2039019DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RNF183 protein" 390ctgcgtggaa tgtctggcc 1939119DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RNF183 protein" 391caagtcagtg acaggctgc 1939219DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RNF183 protein" 392gtctacacgc tggaccttg 1939319DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RNF183 protein" 393gatgcggaac tgagggttg 1939419DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RNF183 protein" 394ctacctgatg gccgtcatc 1939519DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RNF183 protein" 395ccagcagcaa ccgaaaaag 1939618DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RNF183 protein" 396catgcgtgca gggctgca 1839717DNAArtificial SequenceSourceReverse primer for amplifying the nucleotide sequence encoding RNF183 protein 397gtgctgctct cccaggg 1739819DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding RNF183 protein" 398ccgtggaatc gattcccag 1939923DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding RNF183 protein" 399ctgtttctca tatgggtcat tcg 2340041DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RNF183 protein" 400atggctgagc agcagggccg ggagcttgag gctgagtgcc c 4140132DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RNF183 protein" 401gcccacggac actgccatgc tcgccctgct cc 3240237DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RNF183 protein" 402ggaccagccc aagagccgct acttcctgcg ccagcct 3740332DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RNF183 protein" 403cgctggacct tggcccccag cctgggggcc ag 3240428DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RNF183 protein" 404gttcctttgg ggtgtggggt gagtgctg 2840560DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding RNF183 protein" 405cagtggtatc caggaacctg actagcccaa atagcaagtt gcatttctca ctggagctgc 604061413DNAHomo Sapiens 406gcttccggcg gaagcggcct caacaaggga aactttattg ttcccgtggg gcagtcgagg 60atgtcggtga attacgcggc ggggctgtcg ccgtacgcgg acaagggcaa gtgcggcctc 120ccggagatct tcgacccccc ggaggagctg gagcggaagg tgtgggaact ggcgaggctg 180gtctggcagt cttccagtgt ggtgttccac acgggtgccg gcatcagcac tgcctctggc 240atccccgact tcagggacaa actggcagag ctccacggga acatgtttgt ggaagaatgt 300gccaagtgta agacgcagta cgtccgagac acagtcgtgg gcaccatggg cctgaaggcc 360acgggccggc tctgcaccgt ggctaaggca agggggctgc gagcctgcag gggagagctg 420agggacacca tcctagactg ggaggactcc ctgcccgacc gggacctggc actcgccgat 480gaggccagca gatccggccc agcgggaacc tgccgctggc taccaagcgc cggggaggcc 540gcctggtcat cgtcaacctg cagcccacca agcacgaccg ccatgctgac ctccgcatcc 600atggctacgt tgacgaggtc atgacccggc tcatgaagca cctggggctg gagatccccg 660cctgggacgg cccccgtgtg ctggagaggg cgctgccacc cctgccccgc ccgcccaccc 720ccaagctgga gcccaaggag gaatctccca cccggatcaa cggctctatc cccgccggcc 780ccaagcagga gccctgcgcc cagcacaacg gctcagagcc cgccagcccc aaacgggagc 840ggcccaccag ccctgccccc cacagacccc ccaaaagggt gaaggccaag gcggtcccca 900gctgaccagg gtgcttgggg agggtggggc tttttgtaga aactgtggat tctttttctc 960tcgtggtctc actttgttac ttgtttctgt ccccgggagc ctcagggctc tgagagctgt 1020gctccaggcc aggggttaca cctgccctcc gtggtccctc cctgggctcc aggggcctct 1080ggtgcggttc cgggaagaag ccacacccca gaggtgacag gtgagcccct gccacacccc 1140agcctctgac ttgctgtgtt gtccagaggt gaggctgggc cctccctggt ctccagctta 1200aacaggagtg aactccctct gtccccaggg cctcccttct gggcccccta cagcccaccc 1260tacccctcct ccatgggccc tgcaggaggg gagacccacc ttgaagtggg ggatcagtag 1320aggcttgcac tgcctttggg gctggaggga gacgtgggtc caccaggctt ctggaaaagt 1380cctcaatgca ataaaaacaa tttctttctt gca 1413407187PRTHomo Sapiens 407Met Ser Val Asn Tyr Ala Ala Gly Leu Ser Pro Tyr Ala Asp Lys Gly 1 5 10 15 Lys Cys Gly Leu Pro Glu Ile Phe Asp Pro Pro Glu Glu Leu Glu Arg 20 25 30 Lys Val Trp Glu Leu Ala Arg Leu Val Trp Gln Ser Ser Ser Val Val 35 40 45 Phe His Thr Gly Ala Gly Ile Ser Thr Ala Ser Gly Ile Pro Asp Phe 50 55 60 Arg Asp Lys Leu Ala Glu Leu His Gly Asn Met Phe Val Glu Glu Cys 65 70 75 80 Ala Lys Cys Lys Thr Gln Tyr Val Arg Asp Thr Val Val Gly Thr Met 85 90 95 Gly Leu Lys Ala Thr Gly Arg Leu Cys Thr Val Ala Lys Ala Arg Gly 100 105 110 Leu Arg Ala Cys Arg Gly Glu Leu Arg Asp Thr Ile Leu Asp Trp Glu 115 120 125 Asp Ser Leu Pro Asp Arg Asp Leu Ala Leu Ala Asp Glu Ala Ser Arg 130 135 140 Ser Gly Pro Ala Gly Thr Cys Arg Trp Leu Pro Ser Ala Gly Glu Ala 145 150 155 160 Ala Trp Ser Ser Ser Thr Cys Ser Pro Pro Ser Thr Thr Ala Met Leu 165 170 175 Thr Ser Ala Ser Met Ala Thr Leu Thr Arg Ser 180 185 40820DNAArtificial SequenceSourceForward primer for amplifying the nucleotide sequence

encoding SIRT6 protein 408ttgtggaaga atgtgccaag 2040919DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding SIRT6 protein" 409ccttagccac ggtgcagag 1941020DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding SIRT6 protein" 410tcttccagtg tggtgttcca 2041120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding SIRT6 protein" 411ttggcacatt cttccacaaa 2041220DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding SIRT6 protein" 412agctgaggga caccatccta 2041319DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding SIRT6 protein" 413gcaggttgac gatgaccag 1941418DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding SIRT6 protein" 414gcttcctggt cagccaga 1841520DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding SIRT6 protein" 415atgtacccag cgtgatggac 2041618DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding SIRT6 protein" 416gcttcctggt cagccaga 1841720DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding SIRT6 protein" 417ctaggatggt gtccctcagc 2041820DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding SIRT6 protein" 418gagagctgag ggacaccatc 2041920DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding SIRT6 protein" 419gtacccagcg tgatggacag 2042020DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding SIRT6 protein" 420aggatgtcgg tgaattacgc 2042120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding SIRT6 protein" 421aaaggtggtg tcgaacttgg 2042220DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SIRT6 protein" 422tgtaagacgc agtacgtccg 2042320DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SIRT6 protein" 423gacttcaggg acaaactggc 2042418DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SIRT6 protein" 424actgggagga ctccctgc 1842520DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SIRT6 protein" 425tgtaagacgc agtacgtccg 2042620DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SIRT6 protein" 426tgtaagacgc agtacgtccg 2042720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SIRT6 protein" 427tagactggga ggactccctg 2042820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SIRT6 protein" 428gagtctggac catggaggag 2042950DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SIRT6 protein" 429gaagtggggg atcagtagag gcttgcactg cctttggggc tggagggaga 504302859DNAHomo Sapiens 430atgaacctgt gtggcctcat gcccatcttc cccgctcccc tcgaccaggt ggctgacatg 60gaggagctga ccatctggga acagcacacg gccacactgt ccaaggaccc ccgccggggc 120tttggcattg cgatctctgg aggccgagac cggcccggtg gatccatggt tgtatctgac 180gtggtacctg gagggccggc ggagggcagg ctacagacag gcgaccacat cgtcatggtg 240aacggggttt ccatggagaa tgccacctcc gcgtttgcca ttcagatact caagacctgc 300accaagatgg ccaacatcac agtgaaacgt ccccggagga tccacctgcc cgccaccaaa 360gccagcccct ccagcccagg gcgccaggac tcggatgaag acgatgggcc ccagcgggtg 420gaggaggtgg accagggccg gggctatgac ggcgactcat ccagtggctc cggccgctcc 480tgggacgagc gctcccgccg gccgaggcct ggtcgccggg gccgggccgg cagccatggg 540cgtaggagcc caggtggtgg ctctgaggcc aacgggctgg ccctggtgtc cggctttaag 600cggctgccac ggcaggacgt gcagatgaag cctgtgaagt cagtgctggt gaagaggaga 660gacagcgaag agtttggcgt caagctgggc agtcagatct tcatcaagca cattacagat 720tcgggcctgg ctgcccggca ccgtgggctg caggaaggag atctcattct acagatcaac 780ggggtgtcta gccagaacct gtcactgaac gacacccggc gactgattga gaagtcagaa 840gggaagctaa gcctgctggt gctgagagat cgtgggcagt tcctggtgaa cattccgcct 900gctgtcagtg acagcgacag ctcgccattg gaggaaggcg tgaccatggc tgatgagatg 960tcctctcccc ctgcagacat ctcggacctc gcctcggagc tatcgcaggc accaccatcc 1020cacatcccac caccaccccg gcatgctcag cggagccccg aggccagcca gaccgactct 1080cccgtggaga gtccccggct tcggcgggaa agttcagtag attccagaac catctcggaa 1140ccagatgagc aacggtcaga gttgcccagg gaaagcagct atgacatcta cagagtgccc 1200agcagtcaga gcatggagga tcgtgggtac agccccgaca cgcgtgtggt ccgcttcctc 1260aagggcaaga gcatcgggct gcggctggca gggggcaatg acgtgggcat cttcgtgtcc 1320ggggtgcagg cgggcagccc ggccgacggg cagggcatcc aggagggaga tcagattctg 1380caggtgaatg acgtgccatt ccagaacctg acacgggagg aggcagtgca gttcctgctg 1440gggctgccac caggcgagga gatggagctg gtgacgcaga ggaagcagga cattttctgg 1500aaaatggtgc agtcccgcgt gggtgactcc ttctacatcc gcactcactt tgagctggag 1560cccagtccac cgtctggcct gggcttcacc cgtggcgacg tcttccacgt gctggacacg 1620ctgcaccccg gccccgggca gagccacgca cgaggaggcc actggctggc ggtgcgcatg 1680ggtcgtgacc tgcgggagca agagcggggc atcattccca accagagcag ggcggagcag 1740ctggccagcc tggaagctgc ccagagggcc gtgggagtcg ggcccggctc ctccgcgggc 1800tccaatgctc gggccgagtt ctggcggctg cggggtcttc gtcgaggagc caagaagacc 1860actcagcgga gccgtgagga cctctcagct ctgacccgac agggccgcta cccgccctac 1920gaacgagtgg tgttgcgaga agccagtttc aagcgcccgg tagtgatcct gggacccgtg 1980gccgacattg ctatgcagaa gttgactgct gagatgcctg accagtttga aatcgcagag 2040actgtgtcca ggaccgacag cccctccaag atcatcaaac tagacaccgt gcgggtgatt 2100gcagaaaaag acaagcatgc gctcctggat gtgaccccct ccgccatcga gcgcctcaac 2160tatgtgcagt actaccccat tgtggtcttc ttcatccccg agagccggcc ggccctcaag 2220gcactgcgcc agtggctggc gcctgcctcc cgccgcagca cccgtcgcct ctacgcacaa 2280gcccagaagc tgcgaaaaca cagcagccac ctcttcacag ccaccatccc tctgaatggc 2340acgagtgaca cctggtacca ggagctcaag gccatcattc gagagcagca gacgcggccc 2400atctggacgg cggaagatca gctggatggc tccttggagg acaacctaga cctccctcac 2460cacggcctgg ccgacagctc cgctgacctc agctgcgaca gccgcgttaa cagcgactac 2520gagacggacg gcgagggcgg cgcgtacacg gatggcgagg gctacacaga cggcgagggg 2580gggccctaca cggatgtgga tgatgagccc ccggctccag ccctggcccg gtcctcggag 2640cccgtgcagg cagatgagtc ccagagcccg agggatcgtg ggagaatctc ggctcatcag 2700ggggcccagg tggacagccg ccacccccag ggacagtggc gacaggacag catgcgaacc 2760tatgaacggg aagccctgaa gaaaaagttt atgcgagtac atgatgcgga gtcctccgat 2820gaagacggct atgactgggg tccggccact gacctgtga 2859431952PRTHomo Sapiens 431Met Asn Leu Cys Gly Leu Met Pro Ile Phe Pro Ala Pro Leu Asp Gln 1 5 10 15 Val Ala Asp Met Glu Glu Leu Thr Ile Trp Glu Gln His Thr Ala Thr 20 25 30 Leu Ser Lys Asp Pro Arg Arg Gly Phe Gly Ile Ala Ile Ser Gly Gly 35 40 45 Arg Asp Arg Pro Gly Gly Ser Met Val Val Ser Asp Val Val Pro Gly 50 55 60 Gly Pro Ala Glu Gly Arg Leu Gln Thr Gly Asp His Ile Val Met Val 65 70 75 80 Asn Gly Val Ser Met Glu Asn Ala Thr Ser Ala Phe Ala Ile Gln Ile 85 90 95 Leu Lys Thr Cys Thr Lys Met Ala Asn Ile Thr Val Lys Arg Pro Arg 100 105 110 Arg Ile His Leu Pro Ala Thr Lys Ala Ser Pro Ser Ser Pro Gly Arg 115 120 125 Gln Asp Ser Asp Glu Asp Asp Gly Pro Gln Arg Val Glu Glu Val Asp 130 135 140 Gln Gly Arg Gly Tyr Asp Gly Asp Ser Ser Ser Gly Ser Gly Arg Ser 145 150 155 160 Trp Asp Glu Arg Ser Arg Arg Pro Arg Pro Gly Arg Arg Gly Arg Ala 165 170 175 Gly Ser His Gly Arg Arg Ser Pro Gly Gly Gly Ser Glu Ala Asn Gly 180 185 190 Leu Ala Leu Val Ser Gly Phe Lys Arg Leu Pro Arg Gln Asp Val Gln 195 200 205 Met Lys Pro Val Lys Ser Val Leu Val Lys Arg Arg Asp Ser Glu Glu 210 215 220 Phe Gly Val Lys Leu Gly Ser Gln Ile Phe Ile Lys His Ile Thr Asp 225 230 235 240 Ser Gly Leu Ala Ala Arg His Arg Gly Leu Gln Glu Gly Asp Leu Ile 245 250 255 Leu Gln Ile Asn Gly Val Ser Ser Gln Asn Leu Ser Leu Asn Asp Thr 260 265 270 Arg Arg Leu Ile Glu Lys Ser Glu Gly Lys Leu Ser Leu Leu Val Leu 275 280 285 Arg Asp Arg Gly Gln Phe Leu Val Asn Ile Pro Pro Ala Val Ser Asp 290 295 300 Ser Asp Ser Ser Pro Leu Glu Glu Gly Val Thr Met Ala Asp Glu Met 305 310 315 320 Ser Ser Pro Pro Ala Asp Ile Ser Asp Leu Ala Ser Glu Leu Ser Gln 325 330 335 Ala Pro Pro Ser His Ile Pro Pro Pro Pro Arg His Ala Gln Arg Ser 340 345 350 Pro Glu Ala Ser Gln Thr Asp Ser Pro Val Glu Ser Pro Arg Leu Arg 355 360 365 Arg Glu Ser Ser Val Asp Ser Arg Thr Ile Ser Glu Pro Asp Glu Gln 370 375 380 Arg Ser Glu Leu Pro Arg Glu Ser Ser Tyr Asp Ile Tyr Arg Val Pro 385 390 395 400 Ser Ser Gln Ser Met Glu Asp Arg Gly Tyr Ser Pro Asp Thr Arg Val 405 410 415 Val Arg Phe Leu Lys Gly Lys Ser Ile Gly Leu Arg Leu Ala Gly Gly 420 425 430 Asn Asp Val Gly Ile Phe Val Ser Gly Val Gln Ala Gly Ser Pro Ala 435 440 445 Asp Gly Gln Gly Ile Gln Glu Gly Asp Gln Ile Leu Gln Val Asn Asp 450 455 460 Val Pro Phe Gln Asn Leu Thr Arg Glu Glu Ala Val Gln Phe Leu Leu 465 470 475 480 Gly Leu Pro Pro Gly Glu Glu Met Glu Leu Val Thr Gln Arg Lys Gln 485 490 495 Asp Ile Phe Trp Lys Met Val Gln Ser Arg Val Gly Asp Ser Phe Tyr 500 505 510 Ile Arg Thr His Phe Glu Leu Glu Pro Ser Pro Pro Ser Gly Leu Gly 515 520 525 Phe Thr Arg Gly Asp Val Phe His Val Leu Asp Thr Leu His Pro Gly 530 535 540 Pro Gly Gln Ser His Ala Arg Gly Gly His Trp Leu Ala Val Arg Met 545 550 555 560 Gly Arg Asp Leu Arg Glu Gln Glu Arg Gly Ile Ile Pro Asn Gln Ser 565 570 575 Arg Ala Glu Gln Leu Ala Ser Leu Glu Ala Ala Gln Arg Ala Val Gly 580 585 590 Val Gly Pro Gly Ser Ser Ala Gly Ser Asn Ala Arg Ala Glu Phe Trp 595 600 605 Arg Leu Arg Gly Leu Arg Arg Gly Ala Lys Lys Thr Thr Gln Arg Ser 610 615 620 Arg Glu Asp Leu Ser Ala Leu Thr Arg Gln Gly Arg Tyr Pro Pro Tyr 625 630 635 640 Glu Arg Val Val Leu Arg Glu Ala Ser Phe Lys Arg Pro Val Val Ile 645 650 655 Leu Gly Pro Val Ala Asp Ile Ala Met Gln Lys Leu Thr Ala Glu Met 660 665 670 Pro Asp Gln Phe Glu Ile Ala Glu Thr Val Ser Arg Thr Asp Ser Pro 675 680 685 Ser Lys Ile Ile Lys Leu Asp Thr Val Arg Val Ile Ala Glu Lys Asp 690 695 700 Lys His Ala Leu Leu Asp Val Thr Pro Ser Ala Ile Glu Arg Leu Asn 705 710 715 720 Tyr Val Gln Tyr Tyr Pro Ile Val Val Phe Phe Ile Pro Glu Ser Arg 725 730 735 Pro Ala Leu Lys Ala Leu Arg Gln Trp Leu Ala Pro Ala Ser Arg Arg 740 745 750 Ser Thr Arg Arg Leu Tyr Ala Gln Ala Gln Lys Leu Arg Lys His Ser 755 760 765 Ser His Leu Phe Thr Ala Thr Ile Pro Leu Asn Gly Thr Ser Asp Thr 770 775 780 Trp Tyr Gln Glu Leu Lys Ala Ile Ile Arg Glu Gln Gln Thr Arg Pro 785 790 795 800 Ile Trp Thr Ala Glu Asp Gln Leu Asp Gly Ser Leu Glu Asp Asn Leu 805 810 815 Asp Leu Pro His His Gly Leu Ala Asp Ser Ser Ala Asp Leu Ser Cys 820 825 830 Asp Ser Arg Val Asn Ser Asp Tyr Glu Thr Asp Gly Glu Gly Gly Ala 835 840 845 Tyr Thr Asp Gly Glu Gly Tyr Thr Asp Gly Glu Gly Gly Pro Tyr Thr 850 855 860 Asp Val Asp Asp Glu Pro Pro Ala Pro Ala Leu Ala Arg Ser Ser Glu 865 870 875 880 Pro Val Gln Ala Asp Glu Ser Gln Ser Pro Arg Asp Arg Gly Arg Ile 885 890 895 Ser Ala His Gln Gly Ala Gln Val Asp Ser Arg His Pro Gln Gly Gln 900 905 910 Trp Arg Gln Asp Ser Met Arg Thr Tyr Glu Arg Glu Ala Leu Lys Lys 915 920 925 Lys Phe Met Arg Val His Asp Ala Glu Ser Ser Asp Glu Asp Gly Tyr 930 935 940 Asp Trp Gly Pro Ala Thr Asp Leu 945 950 43220DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding TJP3 protein" 432ccctcgacca ggtggctgac 2043319DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding TJP3 protein" 433cctccagaga tcgcaatgc 1943419DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding TJP3 protein" 434gtatctgacg tggtacctg 1943522DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding TJP3 protein" 435ggcaaacgcg gaggtggcat tc 2243620DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding TJP3 protein" 436cggggtttcc atggagaatg 2043719DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding TJP3

protein" 437gcgggcaggt ggatcctcc 1943820DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding TJP3 protein" 438gcaggacgtg cagatgaagc 2043921DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding TJP3 protein" 439cccgaatctg taatgtgctt g 2144021DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding TJP3 protein" 440gtgggctgca ggaaggagat c 2144122DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding TJP3 protein" 441gaactgccca cgatctctca gc 2244219DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding TJP3 protein" 442gatcgtgggc agttcctgg 1944320DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding TJP3 protein" 443gatgtctgca gggggagagg 2044419DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding TJP3 protein" 444caccccggca tgctcagcg 1944519DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding TJP3 protein" 445ccgagatggt tctggaatc 1944619DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding TJP3 protein" 446gagtccccgg cttcggcgg 1944721DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding TJP3 protein" 447cgatcctcca tgctctgact g 2144818DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding TJP3 protein" 448gtgcaggcgg gcagcccg 1844919DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding TJP3 protein" 449gtcctgcttc ctctgcgtc 1945020DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding TJP3 protein" 450cgagagcagc agacgcggcc 2045119DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding TJP3 protein" 451gaggtcagcg gagctgtcg 1945260DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding TJP3 protein" 452cagggacagt ggcgacagga cagcatgcga acctatgaac gggaagccct gaagaaaaag 6045342DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding TJP3 protein" 453gaacagcaca cggccacact gtccaaggac ccccgccggg gc 4245454DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding TJP3 protein" 454accaagatgg ccaacatcac agtgaaacgt ccccggagga tccacctgcc cgcc 5445554DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding TJP3 protein" 455cagtgacagc gacagctcgc cattggagga aggcgtgacc atggctgatg agat 5445654DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding TJP3 protein" 456cgagtggtgt tgcgagaagc cagtttcaag cgcccggtag tgatcctggg accc 5445785PRTArtificial SequenceSource/note="Description of Artificial Sequence Partial recombinant amino acid sequence of TJP3" 457Asp Glu Pro Pro Ala Pro Ala Leu Ala Arg Ser Ser Glu Pro Val Gln 1 5 10 15 Ala Asp Glu Ser Gln Ser Pro Arg Asp Arg Gly Arg Ile Ser Ala His 20 25 30 Gln Gly Ala Gln Val Asp Ser Arg His Pro Gln Gly Gln Trp Arg Gln 35 40 45 Asp Ser Met Arg Thr Tyr Glu Arg Glu Ala Leu Lys Lys Lys Phe Met 50 55 60 Arg Val His Asp Ala Glu Ser Ser Asp Glu Asp Gly Tyr Asp Trp Gly 65 70 75 80 Pro Ala Thr Asp Leu 85 4581938DNAHomo Sapiens 458ggggcgcttc ctggggccgc gcgtccaggg agctgtgccg tccgcccgtc cgtctgcccg 60caggcattgc ccgagccagc cgagccgcca gagccgcggg ccgcgggggt gtcgcgggcc 120caaccccagg atgctcccct gcgcctcctg cctacccggg tctctactgc tctgggcgct 180gctactgttg ctcttgggat cagcttctcc tcaggattct gaagagcccg acagctacac 240ggaatgcaca gatggctatg agtgggaccc agacagccag cactgccggg atgtcaacga 300gtgtctgacc atccctgagg cctgcaaggg ggaaatgaag tgcatcaacc actacggggg 360ctacttgtgc ctgccccgct ccgctgccgt catcaacgac ctacacggcg agggaccccc 420gccaccagtg cctcccgctc aacaccccaa cccctgccca ccaggctatg agcccgacga 480tcaggacagc tgtgtggatg tggacgagtg tgcccaggcc ctgcacgact gtcgccccag 540ccaggactgc cataacttgc ctggctccta tcagtgcacc tgccctgatg gttaccgcaa 600gatcgggccc gagtgtgtgg acatagacga gtgccgctac cgctactgcc agcaccgctg 660cgtgaacctg cctggctcct tccgctgcca gtgcgagccg ggcttccagc tggggcctaa 720caaccgctcc tgtgttgatg tgaacgagtg tgacatgggg gccccatgcg agcagcgctg 780cttcaactcc tatgggacct tcctgtgtcg ctgccaccag ggctatgagc tgcatcggga 840tggcttctcc tgcagtgata ttgatgagtg tagctactcc agctacctct gtcagtaccg 900ctgcgtcaac gagccaggcc gtttctcctg ccactgccca cagggttacc agctgctggc 960cacacgcctc tgccaagaca ttgatgagtg tgagtctggt gcgcaccagt gctccgaggc 1020ccaaacctgt gtcaacttcc atgggggcta ccgctgcgtg gacaccaacc gctgcgtgga 1080gccctacatc caggtctctg agaaccgctg tctctgcccg gcctccaacc ctctatgtcg 1140agagcagcct tcatccattg tgcaccgcta catgaccatc acctcggagc ggagcgtgcc 1200cgctgacgtg ttccagatcc aggcgacctc cgtctacccc ggtgcctaca atgcctttca 1260gatccgtgct ggaaactcgc agggggactt ttacattagg caaatcaaca acgtcagcgc 1320catgctggtc ctcgcccggc cggtgacggg cccccgggag tacgtgctgg acctggagat 1380ggtcaccatg aattccctca tgagctaccg ggccagctct gtactgaggc tcaccgtctt 1440tgtaggggcc tacaccttct gaggagcagg agggagccac cctccctgca gctaccctag 1500ctgaggagcc tgttgtgagg ggcagaatga gaaaggcaat aaagggagaa agaaagtcct 1560ggtggctgag gtgggcgggt cacactgcag gaagcctcag gctggggcag ggtggcactt 1620gggggggcag gccaagttca cctaaatggg ggtctctata tgttcaggcc caggggcccc 1680cattgacagg agctgggagc tctgcaccac gagcttcagt caccccgaga ggagaggagg 1740taacgaggag ggcggactcc aggccccggc ccagagattt ggacttggct ggcttgcagg 1800ggtcctaaga aactccactc tggacagcgc caggaggccc tgggttccat tcctaactct 1860gcctcaaact gtacatttgg ataagcccta gtagttccct gggcctgttt ttctataaaa 1920cgaggcaact ggactgtt 1938459443PRTHomo Sapiens 459Met Leu Pro Cys Ala Ser Cys Leu Pro Gly Ser Leu Leu Leu Trp Ala 1 5 10 15 Leu Leu Leu Leu Leu Leu Gly Ser Ala Ser Pro Gln Asp Ser Glu Glu 20 25 30 Pro Asp Ser Tyr Thr Glu Cys Thr Asp Gly Tyr Glu Trp Asp Pro Asp 35 40 45 Ser Gln His Cys Arg Asp Val Asn Glu Cys Leu Thr Ile Pro Glu Ala 50 55 60 Cys Lys Gly Glu Met Lys Cys Ile Asn His Tyr Gly Gly Tyr Leu Cys 65 70 75 80 Leu Pro Arg Ser Ala Ala Val Ile Asn Asp Leu His Gly Glu Gly Pro 85 90 95 Pro Pro Pro Val Pro Pro Ala Gln His Pro Asn Pro Cys Pro Pro Gly 100 105 110 Tyr Glu Pro Asp Asp Gln Asp Ser Cys Val Asp Val Asp Glu Cys Ala 115 120 125 Gln Ala Leu His Asp Cys Arg Pro Ser Gln Asp Cys His Asn Leu Pro 130 135 140 Gly Ser Tyr Gln Cys Thr Cys Pro Asp Gly Tyr Arg Lys Ile Gly Pro 145 150 155 160 Glu Cys Val Asp Ile Asp Glu Cys Arg Tyr Arg Tyr Cys Gln His Arg 165 170 175 Cys Val Asn Leu Pro Gly Ser Phe Arg Cys Gln Cys Glu Pro Gly Phe 180 185 190 Gln Leu Gly Pro Asn Asn Arg Ser Cys Val Asp Val Asn Glu Cys Asp 195 200 205 Met Gly Ala Pro Cys Glu Gln Arg Cys Phe Asn Ser Tyr Gly Thr Phe 210 215 220 Leu Cys Arg Cys His Gln Gly Tyr Glu Leu His Arg Asp Gly Phe Ser 225 230 235 240 Cys Ser Asp Ile Asp Glu Cys Ser Tyr Ser Ser Tyr Leu Cys Gln Tyr 245 250 255 Arg Cys Val Asn Glu Pro Gly Arg Phe Ser Cys His Cys Pro Gln Gly 260 265 270 Tyr Gln Leu Leu Ala Thr Arg Leu Cys Gln Asp Ile Asp Glu Cys Glu 275 280 285 Ser Gly Ala His Gln Cys Ser Glu Ala Gln Thr Cys Val Asn Phe His 290 295 300 Gly Gly Tyr Arg Cys Val Asp Thr Asn Arg Cys Val Glu Pro Tyr Ile 305 310 315 320 Gln Val Ser Glu Asn Arg Cys Leu Cys Pro Ala Ser Asn Pro Leu Cys 325 330 335 Arg Glu Gln Pro Ser Ser Ile Val His Arg Tyr Met Thr Ile Thr Ser 340 345 350 Glu Arg Ser Val Pro Ala Asp Val Phe Gln Ile Gln Ala Thr Ser Val 355 360 365 Tyr Pro Gly Ala Tyr Asn Ala Phe Gln Ile Arg Ala Gly Asn Ser Gln 370 375 380 Gly Asp Phe Tyr Ile Arg Gln Ile Asn Asn Val Ser Ala Met Leu Val 385 390 395 400 Leu Ala Arg Pro Val Thr Gly Pro Arg Glu Tyr Val Leu Asp Leu Glu 405 410 415 Met Val Thr Met Asn Ser Leu Met Ser Tyr Arg Ala Ser Ser Val Leu 420 425 430 Arg Leu Thr Val Phe Val Gly Ala Tyr Thr Phe 435 440 46020DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 460tgctcttggg atcagcttct 2046120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 461cctcagggat ggtcagacac 2046218DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 462tgcccaccag gctatgag 1846320DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 463caggcaagtt atggcagtcc 2046420DNAArtificial sequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 464aacttgcctg gctcctatca 2046519DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 465gtgctggcag tagcggtag 1946618DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 466ggcctaacaa ccgctcct 1846720DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 467cgacacagga aggtcccata 2046820DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 468tatgggacct tcctgtgtcg 2046920DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 469gatgcagcgg tactgacaga 2047020DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 470gtcagtaccg ctgcatcaac 2047120DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 471cgcaccagac tcacactcat 2047220DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 472gtggagccct acatccaggt 2047320DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding EFEMP2 protein" 473tccgaggtga tggtcatgta 2047450DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EFEMP2 protein" 474ttcatccatt gtgcaccgct acatgaccat cacctcggag cggagcgtgc 5047520DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EFEMP2 protein" 475gaagagcccg acagctacac 2047620DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EFEMP2 protein" 476caggcaagtt atggcagtcc 2047720DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EFEMP2 protein" 477cctgatggtt accgcaagat 2047820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EFEMP2 protein" 478gtgaacgagt gtgacatggg 2047920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EFEMP2 protein" 479atggcttctc ctgcagtgat 2048019DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EFEMP2 protein" 480acgcctctgc caagacatt 1948120DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding EFEMP2 protein" 481atgtcgagag cagccttcat 204822210DNAHomo Sapiens 482agccgcggcc tcaactaaaa gtggccattg acctttcaag ctttcgagca gtgatgcaat 60agaatagtat ttcaaagaaa aatgcttatc gaaattttgg atccggtttt cccgtgattg 120ttaagggttt cttttaaaaa gtaggtcaca tttcaagtag gtcatatttc gggggcgggt 180gcgcagacaa ggagatgagt ttccactaag gccagggggc ctccaacggg gttggaggtg 240agaatcccag gtagggtaga ggtgccgaga tccttccgaa tcccagccct ggggcgtcag 300ccctgcaggg aatggcagag acactctccg gactgaggga accgaggcca gtcaccaagc 360cccttccggg cgcgcaggcg atcagtgggt gaccgcggct gcgagggact ttgtcatccg 420tcctccagga tctggggaga

aagagcccca tcccttctct ctctgccacc atttcggaca 480ccccgcaggg actcgttttg ggattcgcac tgacttcaag gaaggacgcg aacccttctc 540tgaccccagc tcgggcggcc acctgtcttt gccgcggtga cccttctctc atgaccctgc 600ggtgccttga gccctccggg aatggcgggg aagggacgcg gagccagtgg gggaccgcgg 660ggtcggcgga ggagccatcc ccgcaggcgg cgcgtctggc gaaggccctg cgggagctcg 720gtcagacagg atggtactgg ggaagtatga ctgttaatga agccaaagag aaattaaaag 780aggcaccaga aggaactttc ttgattagag atagctcgca ttcagactac ctactaacaa 840tatctgttaa aacatcagct ggaccaacta atcttcgaat cgaataccaa gacggaaaat 900tcagattgga ctctatcata tgtgtcaaat ccaagcttaa acaatttgac agtgtggttc 960atctgatcga ctactatgtt cagatgtgca aggataagcg gacaggtcca gaagcccccc 1020ggaacggcac tgttcacctt tatctgacca aaccgctcta cacgtcagca ccatctctgc 1080agcatctctg taggctcacc attaacaaat gtaccggtgc catctgggga ctgcctttac 1140caacaagact aaaagattac ttggaagaat ataaattcca ggtataaatg tttctctttt 1200tttaaacatg tctcacatag agtatctccg aatgcagcta tgtaaaagag aaccaaaact 1260tgagtgctct ggataactat atggaatgct ttctaagaac agctgaagct aatctaattt 1320aaatttaaca gcttgaagag gtagctaggt gtttaaagtt cctccagata cttttacctg 1380agtgatgctt cccttcctaa ggctgaccaa gacctgttga tccttttaga ttaaaaataa 1440aatgtcgcat gtaaaggctg aagtcgcgtt ttatcagaat gccttgcctt cttaggttct 1500tttccattat gtcaaaggtc caggctccag taggagagaa agaactcctc ataggaatac 1560tgaagaagtg ggaaggaacc aagctgacac aggcctcact gcaatttgat atgcctgctg 1620atcagagtct cttgggcatt ttatattttg cattctgatg tacctaggag ttttgttaaa 1680cagatgatgt atgtgagtat ttatcccatt ttatgcaatt aaccaaatca accaaaaaaa 1740gtgaccatga agtcctgtat ttgtcttttt actacatgta ggaactctca tgtgaatgag 1800tactgtagta atccattcta tgggagcctt atttcagaaa tatttcaaac tggtgcaaat 1860ggaaaagact ttctcttttc ctttaaagct aaagacaaga atatcatgct atacaggtgc 1920aactcaatcc ccgttaataa aaaccaatgt aggtataggc attctaccct ttgaaatagc 1980tgtgtcccaa cctgttgcca ttgatttttt ggaaatggct ttagaaatat ccaagttgtc 2040cttgaattgt ctaaccatgg acataaacag ttgtctccct tctactgtgt agaatacttt 2100gacttaattt tcttccagat acagggggat acctgcctgt ttttcaaagt gtttatttac 2160tgctgttact atttgattag aatgtattaa ataaaaaaaa cctgatttct 2210483198PRTHomo Sapiens 483Met Thr Leu Arg Cys Leu Glu Pro Ser Gly Asn Gly Gly Glu Gly Thr 1 5 10 15 Arg Ser Gln Trp Gly Thr Ala Gly Ser Ala Glu Glu Pro Ser Pro Gln 20 25 30 Ala Ala Arg Leu Ala Lys Ala Leu Arg Glu Leu Gly Gln Thr Gly Trp 35 40 45 Tyr Trp Gly Ser Met Thr Val Asn Glu Ala Lys Glu Lys Leu Lys Glu 50 55 60 Ala Pro Glu Gly Thr Phe Leu Ile Arg Asp Ser Ser His Ser Asp Tyr 65 70 75 80 Leu Leu Thr Ile Ser Val Lys Thr Ser Ala Gly Pro Thr Asn Leu Arg 85 90 95 Ile Glu Tyr Gln Asp Gly Lys Phe Arg Leu Asp Ser Ile Ile Cys Val 100 105 110 Lys Ser Lys Leu Lys Gln Phe Asp Ser Val Val His Leu Ile Asp Tyr 115 120 125 Tyr Val Gln Met Cys Lys Asp Lys Arg Thr Gly Pro Glu Ala Pro Arg 130 135 140 Asn Gly Thr Val His Leu Tyr Leu Thr Lys Pro Leu Tyr Thr Ser Ala 145 150 155 160 Pro Ser Leu Gln His Leu Cys Arg Leu Thr Ile Asn Lys Cys Thr Gly 165 170 175 Ala Ile Trp Gly Leu Pro Leu Pro Thr Arg Leu Lys Asp Tyr Leu Glu 180 185 190 Glu Tyr Lys Phe Gln Val 195 48418DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding SOCS2 protein" 484agtcaccaag ccccttcc 1848520DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding SOCS2 protein" 485gctctttctc cccagatcct 2048620DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding SOCS2 protein" 486gggactgcct ttaccaacaa 2048722DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding SOCS2 protein" 487tttacatagc tgcattcgga ga 2248860DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SOCS2 protein" 488agtgtggttc atctgatcga ctactatgtt cagatgtgca aggataagcg gacaggtcca 6048920DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SOCS2 protein" 489gactttgtca tccgtcctcc 2049025DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding SOCS2 protein" 490acttggaaga atataaattc caggt 254912287DNAHomo Sapiens 491gaatctacaa taagacaaat ttcaaatcaa gttgctccac tatactgcat aagcagttta 60gaatcttaag cagatgcaaa aagaataaag caaatgggag gaaaaaaaag gccgataaag 120tttctggcta caatacaaga gacatatcat taccatatga tctaatgtgg gtgtcagccg 180gattgtgttc attgagggaa accttatttt ttaactgtgc tatggagtag aagcaggagg 240ttttcaacct agtcacagag cagcacctac cccctcctcc tttccacacc tgcaaactct 300tttacttggg ctgaatattt agtgtaatta catctcagct ttgagggctc ctgtggcaaa 360ttcccggatt aaaaggttcc ctggttgtga aaatacatga gataaatcat gaaggccact 420atcatcctcc ttctgcttgc acaagtttcc tgggctggac cgtttcaaca gagaggctta 480tttgacttta tgctagaaga tgaggcttct gggataggcc cagaagttcc tgatgaccgc 540gacttcgagc cctccctagg cccagtgtgc cccttccgct gtcaatgcca tcttcgagtg 600gtccagtgtt ctgatttggg tctggacaaa gtgccaaagg atcttccccc tgacacaact 660ctgctagacc tgcaaaacaa caaaataacc gaaatcaaag atggagactt taagaacctg 720aagaaccttc acgcattgat tcttgtcaac aataaaatta gcaaagttag tcctggagca 780tttacacctt tggtgaagtt ggaacgactt tatctgtcca agaatcagct gaaggaattg 840ccagaaaaaa tgcccaaaac tcttcaggag ctgcgtgccc atgagaatga gatcaccaaa 900gtgcgaaaag ttactttcaa tggactgaac cagatgattg tcatagaact gggcaccaat 960ccgctgaaga gctcaggaat tgaaaatggg gctttccagg gaatgaagaa gctctcctac 1020atccgcattg ctgataccaa tatcaccagc attcctcaag gtcttcctcc ttcccttacg 1080gaattacatc ttgatggcaa caaaatcagc agagttgatg cagctagcct gaaaggactg 1140aataatttgg ctaagttggg attgagtttc aacagcatct ctgctgttga caatggctct 1200ctggccaaca cgcctcatct gagggagctt cacttggaca acaacaagct taccagagta 1260cctggtgggc tggcagagca taagtacatc caggttgtct accttcataa caacaatatc 1320tctgtagttg gatcaagtga cttctgccca cctggacaca acaccaaaaa ggcttcttat 1380tcgggtgtga gtcttttcag caacccggtc cagtactggg agatacagcc atccaccttc 1440agatgtgtct acgtgcgctc tgccattcaa ctcggaaact ataagtaatt ctcaagaaag 1500ccctcatttt tataacctgg caaaatcttg ttaatgtcat tgctaaaaaa taaataaaag 1560ctagatactg gaaacctaac tgcaatgtgg atgttttacc cacatgactt attatgcata 1620aagccaaatt tccagtttaa gtaattgcct acaataaaaa gaaattttgc ctgccatttt 1680cagaatcatc ttttgaagct ttctgttgat gttaactgag ctactagaga tattcttatt 1740tcactaaatg taaaatttgg agtaaatata tatgtcaata tttagtaaag cttttctttt 1800ttaatttcca ggaaaaaata aaaagagtat gagtcttctg taattcattg agcagttagc 1860tcatttgaga taaagtcaaa tgccaaacac tagctctgta ttaatcccca tcattactgg 1920taaagcctca tttgaatgtg tgaattcaat acaggctatg taaaattttt actaatgtca 1980ttattttgaa aaaataaatt taaaaataca ttcaaaatta ctattgtata caagcttaat 2040tgttaatatt ccctaaacac aattttatga agggagaaga cattggtttg ttgacaataa 2100cagtacatct tttcaagttc tcagctattt cttctacctc tccctatctt acatttgagt 2160atggtaactt atgtcatcta tgttgaatgt aagcttataa agcacaaagc atacatttcc 2220tgactggtct agagaactga tgtttcaatt tacccctctg ctaaataaat attaaaacta 2280tcatgtg 2287492359PRTHomo Sapiens 492Met Lys Ala Thr Ile Ile Leu Leu Leu Leu Ala Gln Val Ser Trp Ala 1 5 10 15 Gly Pro Phe Gln Gln Arg Gly Leu Phe Asp Phe Met Leu Glu Asp Glu 20 25 30 Ala Ser Gly Ile Gly Pro Glu Val Pro Asp Asp Arg Asp Phe Glu Pro 35 40 45 Ser Leu Gly Pro Val Cys Pro Phe Arg Cys Gln Cys His Leu Arg Val 50 55 60 Val Gln Cys Ser Asp Leu Gly Leu Asp Lys Val Pro Lys Asp Leu Pro 65 70 75 80 Pro Asp Thr Thr Leu Leu Asp Leu Gln Asn Asn Lys Ile Thr Glu Ile 85 90 95 Lys Asp Gly Asp Phe Lys Asn Leu Lys Asn Leu His Ala Leu Ile Leu 100 105 110 Val Asn Asn Lys Ile Ser Lys Val Ser Pro Gly Ala Phe Thr Pro Leu 115 120 125 Val Lys Leu Glu Arg Leu Tyr Leu Ser Lys Asn Gln Leu Lys Glu Leu 130 135 140 Pro Glu Lys Met Pro Lys Thr Leu Gln Glu Leu Arg Ala His Glu Asn 145 150 155 160 Glu Ile Thr Lys Val Arg Lys Val Thr Phe Asn Gly Leu Asn Gln Met 165 170 175 Ile Val Ile Glu Leu Gly Thr Asn Pro Leu Lys Ser Ser Gly Ile Glu 180 185 190 Asn Gly Ala Phe Gln Gly Met Lys Lys Leu Ser Tyr Ile Arg Ile Ala 195 200 205 Asp Thr Asn Ile Thr Ser Ile Pro Gln Gly Leu Pro Pro Ser Leu Thr 210 215 220 Glu Leu His Leu Asp Gly Asn Lys Ile Ser Arg Val Asp Ala Ala Ser 225 230 235 240 Leu Lys Gly Leu Asn Asn Leu Ala Lys Leu Gly Leu Ser Phe Asn Ser 245 250 255 Ile Ser Ala Val Asp Asn Gly Ser Leu Ala Asn Thr Pro His Leu Arg 260 265 270 Glu Leu His Leu Asp Asn Asn Lys Leu Thr Arg Val Pro Gly Gly Leu 275 280 285 Ala Glu His Lys Tyr Ile Gln Val Val Tyr Leu His Asn Asn Asn Ile 290 295 300 Ser Val Val Gly Ser Ser Asp Phe Cys Pro Pro Gly His Asn Thr Lys 305 310 315 320 Lys Ala Ser Tyr Ser Gly Val Ser Leu Phe Ser Asn Pro Val Gln Tyr 325 330 335 Trp Glu Ile Gln Pro Ser Thr Phe Arg Cys Val Tyr Val Arg Ser Ala 340 345 350 Ile Gln Leu Gly Asn Tyr Lys 355 49319DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DCN protein" 493agctttgagg gctcctgtg 1949420DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DCN protein" 494gcaagcagaa ggaggatgat 2049520DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DCN protein" 495aatgccatct tcgagtggtc 2049621DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DCN protein" 496tgcaggtcta gcagagttgt g 2149721DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DCN protein" 497aaccgaaatc aaagatggag a 2149819DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DCN protein" 498gtccaggtgg gcagaagtc 1949920DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DCN protein" 499aatgccatct tcgagtggtc 2050020DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DCN protein" 500ctgctgattt tgttgccatc 2050120DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DCN protein" 501tggcaacaaa atcagcagag 2050220DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DCN protein" 502gccattgtca acagcagaga 2050320DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DCN protein" 503gggctggcag agcataagta 2050419DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DCN protein" 504gtccaggtgg gcagaagtc 1950521DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DCN protein" 505aaccgaaatc aaagatggag a 2150621DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DCN protein" 506ccaaaggtgt aaatgctcca g 2150720DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DCN protein" 507gagatcacca aagtgcgaaa 2050820DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DCN protein" 508aaagccccat tttcaattcc 2050920DNAArtificial SequenceSource/note="Description of Artificial Sequence Forward primer for amplifying the nucleotide sequence encoding DCN protein" 509aatgccatct tcgagtggtc 2051020DNAArtificial SequenceSource/note="Description of Artificial Sequence Reverse primer for amplifying the nucleotide sequence encoding DCN protein" 510aaagccccat tttcaattcc 2051158DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DCN protein" 511tttaactgtg ctatggagta gaagcaggag gttttcaacc tagtcacaga gcagcacc 5851220DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DCN protein" 512ttcccggatt aaaaggttcc 2051320DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DCN protein" 513aagtgccaaa ggatcttccc 2051420DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DCN protein" 514cctgaagaac cttcacgttg 2051520DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DCN protein" 515tcctccttcc cttacggaat 2051620DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DCN protein" 516atgcagctag cctgaaagga 2051721DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DCN protein" 517catccaggtt gtctaccttc a 2151820DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DCN protein" 518tgaagaacct tcacgcattg 2051920DNAArtificial

SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DCN protein" 519tgtcatagaa ctgggcacca 2052020DNAArtificial SequenceSource/note="Description of Artificial Sequence Probe for detecting a nucleotide molecule having a nucleic acid sequence encoding DCN protein" 520gttctgattt ggaactgggc 2052120DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding ACAA1" 521tcacgggaga agcaggatac 2052218DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding ACAA1" 522cttgctctgg gctcttgc 1852320DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding ACAA1" 523ccagagattg cctgattcct 2052419DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding ACAA1" 524cctgcttctc ccgtgaaat 1952519DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding ACAA1" 525agctggggga catctgtgt 1952620DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding ACAA1" 526cactcagaaa ctgggcgatt 2052720DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding AP1M2" 527cacatcgaag aatgccaatg 2052821DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding AP1M2" 528gctccttgaa gtattcgcag a 2152919DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding AP1M2" 529tgctcttcga gctcactgg 1953019DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding AP1M2" 530cacgcactgg tggaatttt 1953121DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding AP1M2" 531gttcgctaca tcacccagag t 2153219DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding AP1M2" 532gtaaggaagc cccgtgttc 1953320DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding CGN" 533gagcttaccc gaaaagtgga 2053420DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding CGN" 534tctagcttct gccgcttctt 2053520DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding CGN" 535ggagatactc gccaggttga 2053621DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding CGN" 536ccttaagctc ctcctgtgtc c 2153722DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding CGN" 537cctctgtgag gaggaaggtt ag 2253826DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding CGN" 538ttagtagaac cagaagaaac catcac 2653918DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DDR1" 539tagagagcca cccccgta 1854022DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DDR1" 540ccatatagtc cccactgtag gc 2254119DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DDR1" 541ccactctgct ccctgtgtc 1954220DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DDR1" 542ctggcttctc aggctccata 2054320DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DDR1" 543tggggactat taccgtgtgc 2054418DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DDR1" 544acgtcactcg cagtcgtg 1854520DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EPS8L2" 545gcagctcttc tccctcaaca 2054619DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EPS8L2" 546cccactttgc tgcttctcc 1954719DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EPS8L2" 547caagatgagc cccaaggac 1954820DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EPS8L2" 548tgatgacgtt ggagttggaa 2054922DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EPS8L2" 549caaggatgag gtcctagagg tg 2255018DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EPS8L2" 550gatgttgcag ggcacgta 1855120DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding FASTKD1" 551tggaaattct ggggtatcgt 2055220DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding FASTKD1" 552gcatcctttg ttgacagtgc 2055324DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding FASTKD1" 553cctgggaatc aaatatcgaa atag 2455421DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding FASTKD1" 554ccaaaaattc caaagcaatc c 2155525DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding FASTKD1" 555aagaattaac ttttctgcat ttcca 2555622DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding FASTKD1" 556cagaacagac acctcagttg gt 2255718DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding GMIP" 557aaccctggcc atggagac 1855820DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding GMIP" 558ccgccacttc tcaatctcag 2055918DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding GMIP" 559cccagcacca cagtaccc 1856021DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding GMIP" 560ctctgtggag ttggaatctc g 2156118DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding GMIP" 561ctggtggccc atctgttc 1856221DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding GMIP" 562ggttgttggc agacatcttg t 2156325DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding IKBKE" 563acagttcaag aagtctagga tgagg 2556423DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding IKBKE" 564tggctaaatg actgaaattc acc 2356521DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding IKBKE" 565ggacatccct cctctacctc a 2156618DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding IKBKE" 566ggatctcagg cgttccag 1856720DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding IKBKE" 567ctgcctgagg atgagttcct 2056819DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding IKBKE" 568gatgcacaat gccgttctc 1956920DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P2RX4" 569ccgttacgac caaggtcaag 2057020DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P2RX4" 570tgacgaagag ggagttttcc 2057121DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P2RX4" 571tctgtcaaga cgtgtgaggt g 2157223DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P2RX4" 572agtgaagttt tctgcagcct tta 2357321DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P2RX4" 573tctcctggct acaatttcag g 2157420DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P2RX4" 574atgccatagg ccttgatgag 2057521DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P4HB" 575gcttccccca aggaatatac a 2157620DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P4HB" 576tcttcagcca gttcacgatg 2057718DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P4HB" 577gcaggggatg atgacgat 1857819DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P4HB" 578cgtcttcctc catgtctgg 1957919DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P4HB" 579ctggagggca aaatcaagc 1958020DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding P4HB" 580ttcttcccaa caagcacctt 2058122DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PHKG2" 581gcagatccga ctttcagatt tc 2258219DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PHKG2" 582ggggtcccac acaactctc 1958321DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PHKG2" 583ttccagcact gtcaaagacc t 2158420DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PHKG2" 584aaagaagggg tgctgtaggg 2058519DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PHKG2" 585aggctatggc aaggaggtc 1958620DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PHKG2" 586tgcgtaacat caggatctgc 2058720DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPFIBP2" 587aggggataag gagtccctca 2058820DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPFIBP2" 588ctggtgtcct tccagacaca 2058921DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPFIBP2" 589gaatggaagc taaaggccac t 2159020DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPFIBP2" 590atctttcagg gccacctgtt 2059121DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPFIBP2" 591aatcttcgag ggagtggagt c 2159218DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPFIBP2" 592cagggtgtcc ccagtgaa 1859319DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPPIR16A" 593ccctcccagt gttgtcctt 1959418DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPPIR16A" 594ccccactccc aaggaact 1859518DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPPIR16A" 595gagtgctgga cgcctctg 1859618DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPPIR16A" 596ttgaccgcca ggagattg 1859721DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPPIR16A" 597atgccctatg acctgtgtga t 2159819DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding PPPIR16A" 598gatgctgtcc tgggtgatg 1959920DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RASSF7" 599cactagccca agcaataggc 2060020DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RASSF7" 600cactcttgtg gcagcaactg 2060118DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RASSF7" 601cagcctggct ctggtgag

1860219DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RASSF7" 602ggagctctcg gttcagctc 1960318DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RASSF7" 603tctgcctcca gccagaga 1860420DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RASSF7" 604ctccaggagt tctgcgtcat 2060521DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RNF183" 605tccagagtag tctgcctgac c 2160618DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RNF183" 606catcctcagc cacacacg 1860721DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RNF183" 607tccagagtag tctgcctgac c 2160820DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RNF183" 608tgttgttgaa ggggttccag 2060918DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RNF183" 609tctgccaccg tgtctacg 1861020DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding RNF183" 610cggaaacact ccctcaaaga 2061120DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SIRT6" 611agctgaggga caccatccta 2061220DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SIRT6" 612atgtacccag cgtgatggac 2061320DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SIRT6" 613aggatgtcgg tgaattacgc 2061418DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SIRT6" 614agaccagcct cgccagtt 1861518DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SIRT6" 615ggtcagccag aacgtgga 1861620DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SIRT6" 616gtggagctct gccagtttgt 2061718DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding TJP3" 617gtgggcatct tcgtgtcc 1861819DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding TJP3" 618gaatggcacg tcattcacc 1961918DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding TJP3" 619atctggacgg cggaagat 1862021DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding TJP3" 620ggtgagggag gtctaggttg t 2162123DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding TJP3" 621tcatcaagca cattacagat tcg 2362219DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding TJP3" 622ggctagacac cccgttgat 1962320DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EFEMP2" 623actcgcaggg ggacttttac 2062420DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EFEMP2" 624catgagggaa ttcatggtga 2062518DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EFEMP2" 625atcgggatgg cttctcct 1862619DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EFEMP2" 626tgatgcagcg gtactgaca 1962719DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EFEMP2" 627agtaccgctg catcaacga 1962820DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding EFEMP2" 628cgcaccagac tcacactcat 2062918DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SOCS2" 629ggagctcggt cagacagg 1863025DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SOCS2" 630ctaatcaaga aagttccttc tggtg 2563118DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SOCS2" 631cagtcaccaa gccccttc 1863219DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SOCS2" 632aagggatggg gctctttct 1963318DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SOCS2" 633ggagctcggt cagacagg 1863421DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding SOCS2" 634gttccttctg gtgcctcttt t 2163525DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DCN" 635ggagacttta agaacctgaa gaacc 2563620DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DCN" 636cgttccaact tcaccaaagg 2063720DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DCN" 637ctgtcaatgc catcttcgag 2063820DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DCN" 638gatcctttgg cactttgtcc 2063923DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DCN" 639caatatcacc agcattcctc aag 2364020DNAArtificial SequenceSource/note="Description of Artificial Sequence Primer amplifying the nucleotide sequence encoding DCN" 640ctgctgattt tgttgccatc 20

Claims

1. An in vitro method of diagnosing endometrial cancer in a patient comprising: detecting the level of the biomarker IKBKE in a sample from the patient, wherein an increased level of the biomarker IKBKE compared to a control value indicates the existence of endometrial cancer in the patient.

2. The in vitro method of claim 1, further comprising detecting the level of one or more biomarkers selected from the group consisting of GMIP, EFEMP2, and P4HB.

3. The in vitro method of claim 1, further comprising detecting the level of one or more biomarkers selected from the group consisting DDR1, FASTKD1, SIRT6 and PHKG2.

4. The in vitro method of claim 1, further comprising detecting the level of from one or more biomarkers selected from the group consisting of ACAA1, AP1M2, EPS8L2, P2RX4, PPFIBP2, PPP1R16A, CGN, RASSF7, RNF183, TJP3, SOCS2, and DCN.

5. The in vitro method of claim 1, wherein said patient has a risk factor for endometrial cancer or is being screened for endometrial cancer.

6. The in vitro method of claim 1, wherein said sample from said patient is from a patient with abnormal uterine bleeding.

7. The in vitro method of claim 1, wherein said sample from said patient is from a patient having an endometrium with increased thickness.

8. The in vitro method of claim 1, wherein said sample is from a pre-menopausal or post-menopausal patient.

9. The in vitro method of claim 1, wherein said sample is from a peri-menopausal patient.

10. The in vitro method of claim 1, wherein said sample is chosen from a tissue sample, blood and/or serum, and uterine fluid.

11. The in vitro method of claim 10, wherein said sample is a uterine fluid sample.

12. The in vitro method of claim 1, wherein the level of the biomarker(s) is determined by RT-PCR.

13. The in vitro method of 1, wherein the number of biomarkers detected is between 2 to 20.

14. The in vitro method of claim 1, wherein one or more additional biomarkers are detected.

15. The in vitro method of claim 14, wherein said one or more additional biomarkers are chosen from differential diagnosis biomarkers, prognostic biomarkers, biomarkers useful for detecting endometrial cancer, biomarkers for classifying endometrial cancer and auxiliary biomarkers for detecting endometrial cancer.

16. The in vitro method of claim 1, comprising determining the level of the biomarker IKBKE in a uterine fluid aspirate sample from a patient having a symptom or risk factor for endometrial cancer, wherein the biomarker IKBKE is differentially expressed in endometrial cancer as compared to control values representative of individuals not affected by endometrial cancer, wherein if the levels of the biomarker IKBKE is upregulated in the endometrial aspirate sample from the patient then the patient has an increased likelihood of having endometrial cancer.

17. The in vitro method of claim 1, comprising determining the level of RNA expression of the biomarker IKBKE by quantitative PCR in a uterine fluid sample from a human patient having a symptom or risk factor for endometrial cancer, wherein an increased level of the biomarker IKBKE as compared to control indicates the existence of endometrial cancer.

18. The in vitro method of claim 1, wherein P4HB and IKBKE are detected.

19. The in vitro method of claim 1, wherein EFEMP2 and IKBKE are detected.

20. The in vitro method of claim 1, wherein P4HB, GMIP, and IKBKE are detected.

21. The in vitro method of claim 1, wherein a combination of markers is detected, wherein said combination is selected from the group consisting of IKBKE and P4HB; IKBKE and SOCS2; GMIP and IKBKE; GMIP, SOCS2, and IKBKE; GMIP, IKBKE, and P4HB; IKBKE, P4HB, and SOCS2; GMIP, IKBKE, P4HB, and SOCS2; GMIP, SOCS2, IKBKE, and EPS8L2; GMIP, IKBKE, P4HB, and EPS8L2; IKBKE, P4HB, SOCS2, and EPS8L2; GMIP, IKBKE, P4HB, SOCS2, and DDR1; GMIP, IKBKE, P4HB, SOCS2, EPS8L2, and PPP1R16A; GMIP, IKBKE, P4HB, SOCS2, PHKG2, and RASSF7; GMIP, IKBKE, P4HB, SOCS2, EPS8L2, and DDR1; GMIP, IKBKE, P4HB, SOCS2, EPS8L2, PPP1R16A, and DDR1; DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, RASSF7, SIRT6, TJP3, and SOCS2; and DDR1, EPS8L2, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPP1R16A, RASSF7, SIRT6, TJP3, RNF183 and SOCS2; or wherein said combination comprises GMIP, IKBKE, P4HB, SOCS2 and FASTKD1; GMIP, IKBKE, P4HB, SOCS2 and DDR1; GMIP, IKBKE, P4HB, SOCS2 and PHKG2; GMIP, IKBKE, P4HB, SOCS2 and SIRT6; GMIP, IKBKE, P4HB, SOCS2 and ACAA1; GMIP, IKBKE, P4HB, SOCS2 and EFEMP2; GMIP, IKBKE, P4HB, SOCS2 and EPS8L2; GMIP, IKBKE, P4HB, SOCS2 and P2RX4; GMIP, IKBKE, P4HB, SOCS2 and PPFIBP2; GMIP, IKBKE, P4HB, SOCS2 and PPP1R16A; GMIP, IKBKE, P4HB, SOCS2, ACAA1 and FASTKD1; GMIP, IKBKE, P4HB, SOCS2, PHKG2 and FASTKD1; GMIP, IKBKE, P4HB, SOCS2, SIRT6 and FASTKD1; ACAA1, AP1M2, EPS8L2, IKBKE, P2RX4, P4HB, PPFIBP2, PPP1R16A, SIRT6, and EFEMP2; GMIP, IKBKE, P4HB, and EFEMP2; DDR1, FASTKD1, PHKG2, SIRT6, SOCS2, GMIP, IKBKE, P4HB, and EFEMP2; DDR1, FASTKD1, PHKG2, SIRT6, GMIP, IKBKE, P4HB, and EFEMP2; or P4HB, EFEMP2, IKBKE, GMIP, and FASTKD1; or wherein said combination comprises GMIP, IKBKE, P4HB, EFEMP2 and FASTKD1; GMIP, IKBKE, P4HB, EFEMP2 and DDR1; GMIP, IKBKE, P4HB, EFEMP2 and PHKG2; GMIP, IKBKE, P4HB, EFEMP2 and SIRT6; GMIP, IKBKE, P4HB, EFEMP2 and ACAA1; GMIP, IKBKE, P4HB, SOCS2 and EFEMP2; GMIP, IKBKE, P4HB, EFEMP2 and EPS8L2; GMIP, IKBKE, P4HB, EFEMP2 and P2RX4; GMIP, IKBKE, P4HB, EFEMP2 and PPFIBP2; GMIP, IKBKE, P4HB, EFEMP2 and PPP1R16A; GMIP, IKBKE, P4HB, EFEMP2, ACAA1 and FASTKD1; GMIP, IKBKE, P4HB, EFEMP2, PHKG2 and FASTKD1; or GMIP, IKBKE, P4HB, EFEMP2, SIRT6 and FASTKD1.

22. The in vitro method of claim 1, comprising (a) providing a uterine fluid sample obtained from a patient with a pipelle device or syringe wherein the patient has a risk factor or symptom of endometrial cancer; contacting said sample with an agent capable of preserving, preventing, or lessening the degradation of RNA in said uterine fluid sample; (b) determining in said sample the expression level of mRNA corresponding to the marker IKBKE and one or more endogenous genes using quantitative PCR; normalizing the expression level of the biomarker IKBKE with the one or more endogenous genes; and (c) comparing the normalized level of the biomarker IKBKE to a control value wherein differential expression of the biomarker IKBKE indicates endometrial cancer or an increased likelihood of endometrial cancer.

23. The in vitro method of claim 22, wherein said one or more endogenous genes are selected from the group consisting of POLR2A, B2M, PFN1, HMBS, G6PD, and PABPN1.

24. The in vitro method of claim 1, wherein the level of the biomarker IKBKE is the mRNA level.

25. The in vitro method of claim 1, wherein the detecting step is performed using a nucleic acid encoding IKBKE.

26. The in vitro method of claim 1, wherein nucleic acid encoding IKBKE is selected from the group consisting of IKBKE mRNA, IKBKE cDNA, or a complement thereof.

27. The in vitro method of claim 1, wherein the detecting step is performed using a nucleic acid encoding one or more primers that are specific to IKBKE.