Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer

被引：1201

作者：

Barbieri, Christopher E. ^{[1
,2
]}

Baca, Sylvan C. ^{[3
,4
,5
]}

Lawrence, Michael S. ^{[3
]}

Demichelis, Francesca ^{[6
,7
]}

Blattner, Mirjam ^{[1
]}

Theurillat, Jean-Philippe ^{[3
]}

White, Thomas A. ^{[8
]}

Stojanov, Petar ^{[3
]}

Van Allen, Eliezer ^{[3
,5
]}

Stransky, Nicolas ^{[3
]}

Nickerson, Elizabeth ^{[3
]}

Chae, Sung-Suk ^{[1
]}

Boysen, Gunther ^{[1
]}

Auclair, Daniel ^{[3
]}

Onofrio, Robert C. ^{[3
]}

Park, Kyung ^{[1
]}

Kitabayashi, Naoki ^{[1
]}

MacDonald, Theresa Y. ^{[1
]}

Sheikh, Karen ^{[1
]}

Vuong, Terry ^{[1
]}

Guiducci, Candace ^{[3
]}

Cibulskis, Kristian ^{[3
]}

Sivachenko, Andrey ^{[3
]}

Carter, Scott L. ^{[3
]}

Saksena, Gordon ^{[3
]}

Voet, Douglas ^{[3
]}

Hussain, Wasay M. ^{[1
,6
]}

Ramos, Alex H. ^{[3
,4
]}

Winckler, Wendy ^{[3
]}

Redman, Michelle C. ^{[3
]}

Ardlie, Kristin ^{[3
]}

Tewari, Ashutosh K. ^{[2
]}

Mosquera, Juan Miguel ^{[1
]}

Rupp, Niels ^{[9
]}

Wild, Peter J. ^{[9
]}

Moch, Holger ^{[9
]}

Morrissey, Colm ^{[10
,11
]}

Nelson, Peter S. ^{[8
,10
,11
]}

Kantoff, Philip W. ^{[4
,5
]}

Gabriel, Stacey B. ^{[3
]}

Golub, Todd R. ^{[3
,12
,13
,14
]}

Meyerson, Matthew ^{[3
,4
,5
,14
]}

Lander, Eric S. ^{[3
,4
,5
,15
]}

Getz, Gad ^{[3
]}

Rubin, Mark A. ^{[1
,2
]}

Garraway, Levi A. ^{[3
,4
,5
,14
]}

机构：

[1] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA

[2] Weill Cornell Med Coll, Dept Urol, New York, NY USA

[3] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA

[4] Harvard Univ, Sch Med, Boston, MA USA

[5] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[6] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY USA

[7] Univ Trento, Ctr Integrat Biol, Trento, Italy

[8] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98104 USA

[9] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland

[10] Univ Washington, Dept Med, Seattle, WA USA

[11] Univ Washington, Dept Urol, Seattle, WA 98195 USA

[12] Howard Hughes Med Inst, Chevy Chase, MD USA

[13] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[14] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[15] MIT, Dept Biol, Cambridge, MA USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 06期

基金：

美国国家卫生研究院;

关键词：

ETS GENE FUSIONS; FORKHEAD BOX A1; ANDROGEN RECEPTOR; SUPPRESSOR; PROTEIN; DATABASE; TMPRSS2; NKX3.1; HEAD;

D O I：

10.1038/ng.2279

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Prostate cancer is the second most common cancer in men worldwide and causes over 250,000 deaths each year(1). Overtreatment of indolent disease also results in significant morbidity(2). Common genetic alterations in prostate cancer include losses of NKX3.1 (8p21)(3,4) and PTEN (10q23)(5,6), gains of AR (the androgen receptor gene) 7,8 and fusion of ETS family transcription factor genes with androgen-responsive promoters(9-11). Recurrent somatic base-pair substitutions are believed to be less contributory in prostate tumorigenesis(12,13) but have not been systematically analyzed in large cohorts. Here, we sequenced the exomes of 112 prostate tumor and normal tissue pairs. New recurrent mutations were identified in multiple genes, including MED12 and FOXA1. SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6-15% of tumors across multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family gene rearrangements and showed a distinct pattern of genomic alterations. Thus, SPOP mutations may define a new molecular subtype of prostate cancer.

引用

页码：685 / U107

页数：7

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