Open AccessThe Molecular Taxonomy of Primary Prostate Cancer
Author(s) -
Adam Abeshouse,
Jaeil Ahn,
Rehan Akbani,
Adrian Ally,
Samirkumar B. Amin,
Chris Andry,
Matti Annala,
Armen Aprikian,
Joshua Armenia,
Arshi Arora,
J. Todd Auman,
Miruna Balasundaram,
Saianand Balu,
Christopher E. Barbieri,
Thomas Bauer,
Christopher C. Benz,
Alain Bergeron,
Rameen Beroukhim,
Mario Berríos,
Adrian Bivol,
Tom Bodenheimer,
Lori Boice,
Arnoud Boot,
Rodolfo Borges dos Reis,
Paul C. Boutros,
Jay Bowen,
Reanne Bowlby,
Jeffrey M. Boyd,
Robert K. Bradley,
Anne Breggia,
Fadi Brimo,
Christopher A. Bristow,
Denise Brooks,
Bradley M. Broom,
Alan H. Bryce,
Glenn J. Bubley,
Eric Burks,
Yaron S.N. Butterfield,
M. Button,
David Canes,
Carlos Gilberto Carlotti,
Rebecca Carlsen,
Michel Carmel,
Peter R. Carroll,
Scott L. Carter,
Richard W. Cartun,
Brett S. Carver,
June M. Chan,
Matthew T. Chang,
Yu Chen,
Andrew D. Cherniack,
Simone Chevalier,
Lynda Chin,
Juok Cho,
Andy Chu,
Eric Chuah,
Sudha Chudamani,
Kristian Cibulskis,
Giovanni Ciriello,
Amanda Clarke,
Matthew R. Cooperberg,
Niall M. Corcoran,
Anthony J. Costello,
Janet E. Cowan,
Daniel Crain,
Erin Curley,
Kerstin A. David,
John A. Demchok,
Francesca Demichelis,
Noreen Dhalla,
Rajiv Dhir,
Alexandre A. Doueik,
Bettina F. Drake,
Heidi Dvinge,
Natalya Dyakova,
Ina Felau,
Martin L. Ferguson,
Scott Frazer,
Stephen J. Freedland,
Yao Fu,
Stacey Gabriel,
Jianjiong Gao,
Johanna Gardner,
Julie M. Gastier-Foster,
Nils Gehlenborg,
Mark Gerken,
Mark Gerstein,
Gad Getz,
Andrew K. Godwin,
Anuradha Gopalan,
Markus Graefen,
Kiley Graim,
Thomas Gribbin,
Ranabir Guin,
Manaswi Gupta,
Angela Hadjipanayis,
Syed Haider,
Lucie Hamel,
D. Neil Hayes,
David I. Heiman,
Julian M. Hess,
Katherine A. Hoadley,
Andrea Holbrook,
Robert A. Holt,
Antonia H. Holway,
Christopher M. Hovens,
Alan P. Hoyle,
Mei Huang,
Carolyn M. Hutter,
Michael Ittmann,
Lisa Iype,
Joshua M. Stuart,
Corbin D. Jones,
Steven J.M. Jones,
Hartmut Juhl,
André Kahles,
Christopher J. Kane,
L. Sylvia,
Michael Kerger,
Ekta Khurana,
Jaegil Kim,
Robert J. Klein,
Raju Kucherlapati,
Louis Lacombe,
Marc Ladanyi,
Phillip H. Lai,
Peter W. Laird,
Eric S. Lander,
Mathieu Latour,
Michael S. Lawrence,
Kevin Lau,
Tucker W. LeBien,
Darlene Lee,
Semin Lee,
Kjong-Van Lehmann,
Kristen Leraas,
Ignaty Leshchiner,
Robert Leung,
John A. Libertino,
Tara M. Lichtenberg,
Pei Lin,
W. Marston Linehan,
Shiyun Ling,
Scott M. Lippman,
Jia Liu,
Wenbin Liu,
Lucas Lochovsky,
Massimo Loda,
Christopher J. Logothetis,
Laxmi Lolla,
Teri A. Longacre,
Yiling Lu,
Jianhua Luo,
Yussanne Ma,
Harshad S. Mahadeshwar,
David Mallery,
Armaz Mariamidze,
Marco A. Marra,
Michael Mayo,
Shan J. McCall,
Ginette McKercher,
Shaowu Meng,
AnneMarie MesMasson,
Maria J. Merino,
Matthew Meyerson,
Piotr A. Mieczkowski,
Gordon B. Mills,
Kenna Shaw,
Sarah Minner,
Alireza Moinzadeh,
Richard A. Moore,
Scott Morris,
Quaid Morris,
Lisle E. Mose,
Andrew J. Mungall,
Bradley A. Murray,
Jerome Myers,
Rashi Naresh,
Joel B. Nelson,
Mark A. Nelson,
Peter S. Nelson,
Yulia Newton,
Michael S. Noble,
Houtan Noushmehr,
Matti Nykter,
Angeliki Pantazi,
Michael Parfenov,
Peter J. Park,
Joel S. Parker,
Joseph Paulauskis,
Robert Penny,
Charles M. Perou,
Alain Piché,
Todd Pihl,
Peter A. Pinto,
Davide Prandi,
Alexei Protopopov,
Nilsa C. Ramirez,
Arvind Rao,
W. Kimryn Rathmell,
Gunnar Rätsch,
Xiaojia Ren,
Victor E. Reuter,
Sheila M. Reynolds,
Suhn K. Rhie,
Kimberly RiegerChrist,
Jeffrey Roach,
A. Gordon Robertson,
Brian D. Robinson,
Mark A. Rubin,
Fred Saad,
Sara Sadeghi,
Gordon Saksena,
Charles Saller,
Andrew L. Salner,
Francisco Sánchez-Vega,
Chris Sander,
George E. Sandusky,
Guido Sauter,
Andrea Sboner,
Peter T. Scardino,
Eleonora Scarlata,
Jacqueline E. Schein,
Thorsten Schlomm,
Laura S. Schmidt,
Nikolaus Schultz,
Steven E. Schumacher,
Jonathan G. Seidman,
Luciano Neder,
Sahil Seth,
Alexis Sharp,
Candace Shelton,
Troy Shelton,
Hui Shen,
Ronglai Shen,
Mark E. Sherman,
Margi Sheth,
Yan Shi,
Juliann Shih,
Ilya Shmulevich,
Jeffry Simko,
Ronald Simon,
Janae V. Simons,
Payal Sipahimalani,
Tara Skelly,
Heidi J. Sofia,
Matthew G. Soloway,
Xingzhi Song,
Andrea Sorcini,
Carrie Sougnez,
Serghei Stepa,
Chip Stewart,
John Stewart,
Travis Sullivan,
Charlie Sun,
Huandong Sun,
Angela Tam,
Donghui Tan,
Jiabin Tang,
Roy Tarnuzzer,
Katherine Tarvin,
Barry S. Taylor,
Patrick Teebagy,
Imelda Tenggara,
Bernard Têtu,
Ashutosh Tewari,
Nina Thiessen,
Timothy C. Thompson,
Leigh B. Thorne,
Daniela Pretti da Cunha Tirapelli,
Scott A. Tomlins,
Felipe Amstalden Trevisan,
Patricia Troncoso,
Lawrence D. True,
Maria Christina Tsourlakis,
Svitlana Tyekucheva,
Eliezer M. Van Allen,
David Van Den Berg,
Umadevi Veluvolu,
Roel R.G. Verhaak,
Cathy D. Vocke,
Doug Voet,
Yunhu Wan,
Qingguo Wang,
Wenyi Wang,
Linghua Wang,
Nils Weinhold,
John N. Weinstein,
Daniel J. Weisenberger,
Matthew D. Wilkerson,
Lisa Wise,
John S. Witte,
Chia-Chin Wu,
Junyuan Wu,
Ye Wu,
Andrew Wei Xu,
Shalini S. Yadav,
Liming Yang,
Lixing Yang,
Christina Yau,
Huihui Ye,
Peggy Yena,
Thomas Zeng,
Jean C. Zenklusen,
Hailei Zhang,
Jianhua Zhang,
Jiashan Zhang,
Yaoguang Zhang,
義夫 田中,
Kelsey Zhu,
Erik Zmuda
Publication year - 2015
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2015.10.025
Subject(s) - biology , primary (astronomy) , prostate cancer , taxonomy (biology) , computational biology , cancer , molecular taxonomy , prostate , genetics , ecology , gene , phylogenetics , physics , astronomy
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.
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