Integrated genomic characterization of endometrial carcinoma

被引：4030

作者：

Getz, Gad ^{[1
]}

Gabriel, Stacey B. ^{[1
]}

Cibulskis, Kristian ^{[1
]}

Lander, Eric ^{[1
]}

Sivachenko, Andrey ^{[1
]}

Sougnez, Carrie ^{[1
]}

Lawrence, Mike ^{[1
]}

Kandoth, Cyriac ^{[2
]}

Dooling, David ^{[2
]}

Fulton, Robert ^{[2
]}

Fulton, Lucinda ^{[2
]}

Kalicki-Veizer, Joelle ^{[2
]}

McLellan, Michael D. ^{[2
]}

O'Laughlin, Michelle ^{[2
]}

Schmidt, Heather ^{[2
]}

Wilson, Richard K. ^{[2
]}

Ye, Kai ^{[2
]}

Ding, Li ^{[2
]}

Mardis, Elaine R. ^{[2
,3
]}

Ally, Adrian ^{[3
]}

Balasundaram, Miruna ^{[3
]}

Birol, Inanc ^{[3
]}

Butterfield, Yaron S. N. ^{[3
]}

Carlsen, Rebecca ^{[3
]}

Carter, Candace ^{[3
]}

Chu, Andy ^{[3
]}

Chuah, Eric ^{[3
]}

Chun, Hye-Jung E. ^{[3
]}

Dhalla, Noreen ^{[3
]}

Guin, Ranabir ^{[3
]}

Hirst, Carrie ^{[3
]}

Holt, Robert A. ^{[3
]}

Jones, Steven J. M. ^{[3
]}

Lee, Darlene ^{[3
]}

Li, Haiyan I. ^{[3
]}

Marra, Marco A. ^{[3
]}

Mayo, Michael ^{[3
]}

Moore, Richard A. ^{[3
]}

Mungall, Andrew J. ^{[3
]}

Plettner, Patrick ^{[3
]}

Schein, Jacqueline E. ^{[3
]}

Sipahimalani, Payal ^{[3
]}

Tam, Angela ^{[3
]}

Varhol, Richard J. ^{[3
]}

Robertson, A. Gordon ^{[3
]}

Pashtan, Itai ^{[1
]}

Saksena, Gordon ^{[1
]}

Onofrio, Robert C. ^{[1
]}

Schumacher, Steven E. ^{[1
]}

Tabak, Barbara ^{[1
]}

机构：

[1] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02139 USA

[2] Washington Univ, Genome Inst, St Louis, MO 63108 USA

[3] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada

[4] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[5] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Inst Appl Canc Sci, Houston, TX 77054 USA

[8] Boston Childrens Hosp, Informat Program, Boston, MA 02115 USA

[9] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA

[10] Univ N Carolina, Inst Pharmacogenet & Individualized Therapy, Chapel Hill, NC 27599 USA

[11] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[12] Univ N Carolina, Div Med Oncol, Dept Internal Med, Chapel Hill, NC 27599 USA

[13] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA

[14] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[15] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA

[16] Univ N Carolina, Res Comp Ctr, Chapel Hill, NC 27599 USA

[17] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Canc Biol Div, Baltimore, MD 21231 USA

[18] Univ So Calif, Epigenome Ctr, Los Angeles, CA 90089 USA

[19] Inst Syst Biol, Seattle, WA 98109 USA

[20] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA

[21] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[22] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA

[23] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA

[24] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA

[25] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA

[26] Buck Inst Age Res, Novato, CA 94945 USA

[27] Univ Texas MD Anderson Canc Ctr, Canc Genom Core Lab, Houston, TX 77054 USA

[28] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[29] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[30] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[31] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA

[32] Ohio State Univ, Columbus, OH 43210 USA

[33] Asterand, Detroit, MI 48202 USA

[34] Univ N Carolina, Chapel Hill, NC 27599 USA

[35] British Columbia Canc Agcy, OvCaRe British Columbia, Vancouver, BC V5Z 4E6, Canada

[36] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada

[37] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA

[38] Helen F Graham Canc Ctr Christiana Care, Newark, DC 19713 USA

[39] Cureline Inc, San Francisco, CA 94080 USA

[40] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC 27710 USA

[41] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA

[42] Univ Calif Irvine, Med Ctr, Orange, CA 92868 USA

[43] Nationwide Childrens Hosp, Res Inst, GOG Tissue Bank, Columbus, OH 43205 USA

[44] Int Genom Consortium, Phoenix, AZ 85004 USA

[45] Mayo Clin, Div Gynecol Oncol, Dept OB Gyn, Rochester, MN 55905 USA

[46] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA

[47] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA

[48] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[49] NN Blokhin Russian Canc Res Ctr RAMS, Moscow 115478, Russia

[50] Ontario Inst Canc Res, Ontario Tumour Bank, Toronto, ON M5G 0A3, Canada

来源：

NATURE | 2013年 / 497卷 / 7447期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

MICROSATELLITE INSTABILITY; SOMATIC MUTATIONS; HIGH-FREQUENCY; LUNG-CANCER; PROTEIN; PIK3R1; TUMORS; GRADE; MODEL;

D O I：

10.1038/nature12113

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine seroustumours and similar to 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.

引用

页码：67 / 73

页数：7

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