The Molecular Taxonomy of Primary Prostate Cancer

被引：2315

作者：

Abeshouse, Adam ^{[1
]}

Ahn, Jaeil ^{[1
]}

Akbani, Rehan ^{[1
]}

Ally, Adrian ^{[1
]}

Amin, Samirkumar ^{[1
]}

Andry, Christopher D. ^{[1
]}

Annala, Matti ^{[1
]}

Aprikian, Armen ^{[1
]}

Armenia, Joshua ^{[1
]}

Arora, Arshi ^{[1
]}

Auman, J. Todd ^{[1
]}

Balasundaram, Miruna ^{[1
]}

Balu, Saianand ^{[1
]}

Barbieri, Christopher E. ^{[1
]}

Bauer, Thomas ^{[1
]}

Benz, Christopher C. ^{[1
]}

Bergeron, Alain ^{[1
]}

Beroukhim, Rameen ^{[1
]}

Berrios, Mario ^{[1
]}

Bivol, Adrian ^{[1
]}

Bodenheimer, Tom ^{[1
]}

Boice, Lori ^{[1
]}

Bootwalla, Moiz S. ^{[1
]}

dos Reis, Rodolfo Borges ^{[1
]}

Boutros, Paul C. ^{[1
]}

Bowen, Jay ^{[1
]}

Bowlby, Reanne ^{[1
]}

Boyd, Jeffrey ^{[1
]}

Bradley, Robert K. ^{[1
]}

Breggia, Anne ^{[1
]}

Brimo, Fadi ^{[1
]}

Bristow, Christopher A. ^{[1
]}

Brooks, Denise ^{[1
]}

Broom, Bradley M. ^{[1
]}

Bryce, Alan H. ^{[1
]}

Bubley, Glenn ^{[1
]}

Burks, Eric ^{[1
]}

Butterfield, Yaron S. N. ^{[1
]}

Button, Michael ^{[1
]}

Canes, David ^{[1
]}

Carlotti, Carlos G. ^{[1
]}

Carlsen, Rebecca ^{[1
]}

Carmel, Michel ^{[1
]}

Carroll, Peter R. ^{[1
]}

Carter, Scott L. ^{[1
]}

Cartun, Richard ^{[1
]}

Carver, Brett S. ^{[1
]}

Chan, June M. ^{[1
]}

Chang, Matthew T. ^{[1
]}

Chen, Yu ^{[1
]}

机构：

[1] NCI, Canc Genome Atlas Program Off, NIH, Bethesda, MD 20892 USA

来源：

CELL | 2015年 / 163卷 / 04期

关键词：

ETS GENE FUSIONS; ACTIVE ANDROGEN RECEPTOR; DNA METHYLATION; RADICAL PROSTATECTOMY; EXPRESSION PROFILES; WHOLE-GENOME; MUTATIONS; SPOP; RECURRENCE; REARRANGEMENTS;

D O I：

10.1016/j.cell.2015.10.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.

引用

页码：1011 / 1025

页数：15

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