Integrated Genomic Characterization of Endometrial Carcinoma The Cancer Genome Atlas Research Network Summary

We performed an integrated genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumors and ~25 % of high-grade endometrioid tumors have extensive copy number alterations, few DNA methylation changes, low ER/PR levels, and frequent TP53 mutations. Most endometrioid tumors have few copy number alterations or TP53 mutations but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A, KRAS and novel mutations in the SWI/SNF gene ARID5B. A subset of endometrioid tumors we identified had a dramatically increased transversion mutation frequency, and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy number low, and copy number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may impact post-surgical adjuvant treatment for women with aggressive tumors. Endometrial cancer arises from the lining of the uterus. It is the fourth most common malignancy among women in the United States, with an estimated 47,000 new cases and 8,000 deaths in 2012.1 Most patients present with low-grade, early-stage disease. The majority of patients with more aggressive, high-grade tumors who have disease spread beyond the uterus will progress within 1 year.2,3 Endometrial cancers have been broadly classified into two groups.4 Type I endometrioid tumors are linked to estrogen excess, obesity, hormone-receptor positivity, and favorable prognosis compared with type II, Correspondence and requests for materials should be addressed to D. Levin