The genomics and genetics of endometrial cancer

enomics and genetics of endometrial cancer Review (2452) Total Article Views Authors: O'Hara AJ, Bell DW Published Date March 2012 Volume 2012:2 Pages 33 - 47 DOI: http://dx.doi.org/10.2147/AGG.S28953 Received: 07 December 2011 Accepted: 04 January 2012 Published: 07 March 2012 Andrea J O’Hara, Daphne W Bell National Human Genome Research Institute, Cancer Genetics Branch, National Institutes of Health, Bethesda, MD, USA Abstract: Most sporadic endometrial cancers (ECs) can be histologically classified as endometrioid, serous, or clear cell. Each histotype has a distinct natural history, clinical behavior, and genetic etiology. Endometrioid ECs have an overall favorable prognosis. They are typified by high frequency genomic alterations affecting PIK3CA, PIK3R1, PTEN, KRAS, FGFR2, ARID1A (BAF250a), and CTNNB1 (β-catenin), as well as epigenetic silencing of MLH1 resulting in microsatellite instability. Serous and clear cell ECs are clinically aggressive tumors that are rare at presentation but account for a disproportionate fraction of all endometrial cancer deaths. Serous ECs tend to be aneuploid and are typified by frequent genomic alterations affecting TP53 (p53), PPP2R1A, HER-2/ERBB2, PIK3CA, and PTEN; additionally, they display dysregulation of E-cadherin, p16, cyclin E, and BAF250a. The genetic etiology of clear cell ECs resembles that of serous ECs, but it remains relatively poorly defined. A detailed discussion of the characteristic patterns of genomic alterations that distinguish the three major histotypes of endometrial cancer is reviewed herein.