| 6. | Nature. 2013 May 2;497(7447):67-73. doi: 10.1038/nature12113.Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA. Collaborators: Getz G, Gabriel SB, Cibulskis K, Lander E, Sivachenko A, Sougnez C, Lawrence M, Kandoth C, Dooling D, Fulton R, Fulton L, Kalicki-Veizer J, McLellan MD, O'Laughlin M, Schmidt H, Wilson RK, Ye K, Ding L, Mardis ER, Ally A, Balasundaram M, Birol I, Butterfield YS, Carlsen R, Carter C, Chu A, Chuah E, Chuah HJ, Dhalla N, Guin R, Hirst C, Holt RA, Jones SJ, Lee D, Li HI, Marra MA, Mayo M, Moore RA, Mungall AJ, Plettner P, Schein JE, Sipahimalani P, Tam A, Varhol RJ, Robertson A, Cherniack AD, Pashtan I, Saksena G, Onofrio RC, Schumacher SE, Tabak B, Carter SL, Hernandez B, Gentry J, Salvesen HB, Ardlie K, Getz G, Winckler W, Beroukhim R, Gabriel SB, Meyerson M, Hadjipanayis A, Lee S, Mahadeshwar HS, Park P, Protopopov A, Ren X, Seth S, Song X, Tang J, Xi R, Yang L, Zeng D, Kucherlapati R, Chin L, Zhang J, Auman T, Balu S, Bodenheimer T, Buda E, Hayes D, Hoyle AP, Jefferys SR, Jones CD, Meng S, Mieczkowski PA, Mose LE, Parker JS, Perou CM, Roach J, Shi Y, Simons JV, Soloway MG, Tan D, Topal MD, Waring S, Wu J, Hoadley KA, Baylin SB, Bootwalla MS, Lai PH, Triche TJ Jr, Van Den Berg DJ, Weisenberger DJ, Laird PW, Shen H, Chin L, Zhang J, Getz G, Cho J, DiCara D, Frazer S, Heiman D, Jing R, Lin P, Mallard W, Stojanov P, Voet D, Zhang H, Zou L, Noble M, Lawrence M, Reynolds SM, Shmulevich I, Aksoy B, Antipin Y, Ciriello G, Dresdner G, Gao J, Gross B, Jacobsen A, Ladanyi M, Reva B, Sander C, Sinha R, Sumer S, Taylor BS, Cerami E, Weinhold N, Schultz N, Shen R, Benz S, Goldstein T, Haussler D, Ng S, Szeto C, Stuart J, Benz CC, Yau C, Zhang W, Annala M, Broom BM, Casasent TD, Ju Z, Liang H, Liu G, Lu Y, Unruh AK, Wakefield C, Weinstein JN, Zhang N, Liu Y, Broaddus R, Akbani R, Mills GB, Adams C, Barr T, Black AD, Bowen J, Deardurff J, Frick J, Gastier-Foster JM, Grossman T, Harper HA, Hart-Kothari M, Helsel C, Hobensack A, Kuck H, Kneile K, Leraas KM, Lichtenberg TM, McAllister C, Pyatt RE, Ramirez NC, Tabler TR, Vanhoose N, White P, Wise L, Zmuda E, Barnabas N, Berry-Green C, Blanc V, Boice L, Button M, Farkas A, Green A, MacKenzie J, Nicholson D, Kalloger SE, Gilks CB, Karlan BY, Lester J, Orsulic S, Borowsky M, Cadungog M, Czerwinski C, Huelsenbeck-Dill L, Iacocca M, Petrelli N, Rabeno B, Witkin G, Nemirovich-Danchenko E, Potapova O, Rotin D, Berchuck A, Birrer M, DiSaia P, Monovich L, Curley E, Gardner J, Mallery D, Penny R, Dowdy SC, Winterhoff B, Dao L, Gostout B, Meuter A, Teoman A, Dao F, Olvera N, Bogomolniy F, Garg K, Soslow RA, Levine DA, Abramov M, Bartlett JM, Kodeeswaran S, Parfitt J, Moiseenko F, Clarke BA, Goodman MT, Carney ME, Matsuno RK, Fisher J, Huang M, Rathmell W, Thorne L, Van Le L, Dhir R, Edwards R, Elishaev E, Zorn K, Broaddus R, Goodfellow PJ, Mutch D, Schultz N, Liu Y, Akbani R, Cherniack AD, Cerami E, Weinhold N, Shen H, Hoadley KA, Kahn AB, Bell DW, Pollock PM, Wang C, Wheeler DA, Shinbrot E, Karlan BY, Berchuck A, Dowdy SC, Winterhoff B, Goodman MT, Robertson A, Beroukhim R, Pashtan I, Salvesen HB, Laird PW, Noble M, Stuart J, Ding L, Kandoth C, Gilks C, Soslow RA, Goodfellow PJ, Mutch D, Broaddus R, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA, Ayala B, Chu AL, Jensen MA, Kothiyal P, Pihl TD, Pontius J, Pot DA, Snyder EE, Srinivasan D, Kahn AB, Shaw KR, Sheth M, Davidsen T, Eley G, Ferguson ML, Demchok JA, Yang L, Guyer MS, Ozenberger BA, Sofia HJ. AbstractWe performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly 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 affect post-surgical adjuvant treatment for women with aggressive tumours. |
