Abstract
Summary 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1011-1025 |
| Number of pages | 15 |
| Journal | Cell |
| Volume | 163 |
| Issue number | 4 |
| DOIs | |
| State | Published - Nov 5 2015 |
| Externally published | Yes |
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
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In: Cell, Vol. 163, No. 4, 05.11.2015, p. 1011-1025.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - The Molecular Taxonomy of Primary Prostate Cancer
AU - Abeshouse, Adam
AU - Ahn, Jaeil
AU - Akbani, Rehan
AU - Ally, Adrian
AU - Amin, Samirkumar
AU - Andry, Christopher D.
AU - Annala, Matti
AU - Aprikian, Armen
AU - Armenia, Joshua
AU - Arora, Arshi
AU - Auman, J. Todd
AU - Balasundaram, Miruna
AU - Balu, Saianand
AU - Barbieri, Christopher E.
AU - Bauer, Thomas
AU - Benz, Christopher C.
AU - Bergeron, Alain
AU - Beroukhim, Rameen
AU - Berrios, Mario
AU - Bivol, Adrian
AU - Bodenheimer, Tom
AU - Boice, Lori
AU - Bootwalla, Moiz S.
AU - Borges Dos Reis, Rodolfo
AU - Boutros, Paul C.
AU - Bowen, Jay
AU - Bowlby, Reanne
AU - Boyd, Jeffrey
AU - Bradley, Robert K.
AU - Breggia, Anne
AU - Brimo, Fadi
AU - Bristow, Christopher A.
AU - Brooks, Denise
AU - Broom, Bradley M.
AU - Bryce, Alan H.
AU - Bubley, Glenn
AU - Burks, Eric
AU - Butterfield, Yaron S.N.
AU - Button, Michael
AU - Canes, David
AU - Carlotti, Carlos G.
AU - Carlsen, Rebecca
AU - Carmel, Michel
AU - Carroll, Peter R.
AU - Carter, Scott L.
AU - Cartun, Richard
AU - Carver, Brett S.
AU - Chan, June M.
AU - Chang, Matthew T.
AU - Chen, Yu
AU - Cherniack, Andrew D.
AU - Chevalier, Simone
AU - Chin, Lynda
AU - Cho, Juok
AU - Chu, Andy
AU - Chuah, Eric
AU - Chudamani, Sudha
AU - Cibulskis, Kristian
AU - Ciriello, Giovanni
AU - Clarke, Amanda
AU - Cooperberg, Matthew R.
AU - Corcoran, Niall M.
AU - Costello, Anthony J.
AU - Cowan, Janet
AU - Crain, Daniel
AU - Curley, Erin
AU - David, Kerstin
AU - Demchok, John A.
AU - Demichelis, Francesca
AU - Dhalla, Noreen
AU - Dhir, Rajiv
AU - Doueik, Alexandre
AU - Drake, Bettina
AU - Dvinge, Heidi
AU - Dyakova, Natalya
AU - Felau, Ina
AU - Ferguson, Martin L.
AU - Frazer, Scott
AU - Freedland, Stephen
AU - Fu, Yao
AU - Gabriel, Stacey B.
AU - Gao, Jianjiong
AU - Gardner, Johanna
AU - Gastier-Foster, Julie M.
AU - Gehlenborg, Nils
AU - Gerken, Mark
AU - Gerstein, Mark B.
AU - Getz, Gad
AU - Godwin, Andrew K.
AU - Gopalan, Anuradha
AU - Graefen, Markus
AU - Graim, Kiley
AU - Gribbin, Thomas
AU - Guin, Ranabir
AU - Gupta, Manaswi
AU - Hadjipanayis, Angela
AU - Haider, Syed
AU - Hamel, Lucie
AU - Hayes, D. Neil
AU - Heiman, David I.
AU - Hess, Julian
AU - Hoadley, Katherine A.
AU - Holbrook, Andrea H.
AU - Holt, Robert A.
AU - Holway, Antonia
AU - Hovens, Christopher M.
AU - Hoyle, Alan P.
AU - Huang, Mei
AU - Hutter, Carolyn M.
AU - Ittmann, Michael
AU - Iype, Lisa
AU - Jefferys, Stuart R.
AU - Jones, Corbin D.
AU - Jones, Steven J.M.
AU - Juhl, Hartmut
AU - Kahles, Andre
AU - Kane, Christopher J.
AU - Kasaian, Katayoon
AU - Kerger, Michael
AU - Khurana, Ekta
AU - Kim, Jaegil
AU - Klein, Robert J.
AU - Kucherlapati, Raju
AU - Lacombe, Louis
AU - Ladanyi, Marc
AU - Lai, Phillip H.
AU - Laird, Peter W.
AU - Lander, Eric S.
AU - Latour, Mathieu
AU - Lawrence, Michael S.
AU - Lau, Kevin
AU - Lebien, Tucker
AU - Lee, Darlene
AU - Lee, Semin
AU - Lehmann, Kjong Van
AU - Leraas, Kristen M.
AU - Leshchiner, Ignaty
AU - Leung, Robert
AU - Libertino, John A.
AU - Lichtenberg, Tara M.
AU - Lin, Pei
AU - Linehan, W. Marston
AU - Ling, Shiyun
AU - Lippman, Scott M.
AU - Liu, Jia
AU - Liu, Wenbin
AU - Lochovsky, Lucas
AU - Loda, Massimo
AU - Logothetis, Christopher
AU - Lolla, Laxmi
AU - Longacre, Teri
AU - Lu, Yiling
AU - Luo, Jianhua
AU - Ma, Yussanne
AU - Mahadeshwar, Harshad S.
AU - Mallery, David
AU - Mariamidze, Armaz
AU - Marra, Marco A.
AU - Mayo, Michael
AU - McCall, Shannon
AU - McKercher, Ginette
AU - Meng, Shaowu
AU - Mes-Masson, Anne Marie
AU - Merino, Maria J.
AU - Meyerson, Matthew
AU - Mieczkowski, Piotr A.
AU - Mills, Gordon B.
AU - Shaw, Kenna R.Mills
AU - Minner, Sarah
AU - Moinzadeh, Alireza
AU - Moore, Richard A.
AU - Morris, Scott
AU - Morrison, Carl
AU - Mose, Lisle E.
AU - Mungall, Andrew J.
AU - Murray, Bradley A.
AU - Myers, Jerome B.
AU - Naresh, Rashi
AU - Nelson, Joel
AU - Nelson, Mark A.
AU - Nelson, Peter S.
AU - Newton, Yulia
AU - Noble, Michael S.
AU - Noushmehr, Houtan
AU - Nykter, Matti
AU - Pantazi, Angeliki
AU - Parfenov, Michael
AU - Park, Peter J.
AU - Parker, Joel S.
AU - Paulauskis, Joseph
AU - Penny, Robert
AU - Perou, Charles M.
AU - Piché, Alain
AU - Pihl, Todd
AU - Pinto, Peter A.
AU - Prandi, Davide
AU - Protopopov, Alexei
AU - Ramirez, Nilsa C.
AU - Rao, Arvind
AU - Rathmell, W. Kimryn
AU - Rätsch, Gunnar
AU - Ren, Xiaojia
AU - Reuter, Victor E.
AU - Reynolds, Sheila M.
AU - Rhie, Suhn K.
AU - Rieger-Christ, Kimberly
AU - Roach, Jeffrey
AU - Robertson, A. Gordon
AU - Robinson, Brian
AU - Rubin, Mark A.
AU - Saad, Fred
AU - Sadeghi, Sara
AU - Saksena, Gordon
AU - Saller, Charles
AU - Salner, Andrew
AU - Sanchez-Vega, Francisco
AU - Sander, Chris
AU - Sandusky, George
AU - Sauter, Guido
AU - Sboner, Andrea
AU - Scardino, Peter T.
AU - Scarlata, Eleonora
AU - Schein, Jacqueline E.
AU - Schlomm, Thorsten
AU - Schmidt, Laura S.
AU - Schultz, Nikolaus
AU - Schumacher, Steven E.
AU - Seidman, Jonathan
AU - Neder, Luciano
AU - Seth, Sahil
AU - Sharp, Alexis
AU - Shelton, Candace
AU - Shelton, Troy
AU - Shen, Hui
AU - Shen, Ronglai
AU - Sherman, Mark
AU - Sheth, Margi
AU - Shi, Yan
AU - Shih, Juliann
AU - Shmulevich, Ilya
AU - Simko, Jeffry
AU - Simon, Ronald
AU - Simons, Janae V.
AU - Sipahimalani, Payal
AU - Skelly, Tara
AU - Sofia, Heidi J.
AU - Soloway, Matthew G.
AU - Song, Xingzhi
AU - Sorcini, Andrea
AU - Sougnez, Carrie
AU - Stepa, Serghei
AU - Stewart, Chip
AU - Stewart, John
AU - Stuart, Joshua M.
AU - Sullivan, Travis B.
AU - Sun, Charlie
AU - Sun, Huandong
AU - Tam, Angela
AU - Tan, Donghui
AU - Tang, Jiabin
AU - Tarnuzzer, Roy
AU - Tarvin, Katherine
AU - Taylor, Barry S.
AU - Teebagy, Patrick
AU - Tenggara, Imelda
AU - Têtu, Bernard
AU - Tewari, Ashutosh
AU - Thiessen, Nina
AU - Thompson, Timothy
AU - Thorne, Leigh B.
AU - Tirapelli, Daniela P.
AU - Tomlins, Scott A.
AU - Trevisan, Felipe Amstalden
AU - Troncoso, Patricia
AU - True, Lawrence D.
AU - Tsourlakis, Maria Christina
AU - Tyekucheva, Svitlana
AU - Van Allen, Eliezer
AU - Van Den Berg, David J.
AU - Veluvolu, Umadevi
AU - Verhaak, Roel
AU - Vocke, Cathy D.
AU - Voet, Doug
AU - Wan, Yunhu
AU - Wang, Qingguo
AU - Wang, Wenyi
AU - Wang, Zhining
AU - Weinhold, Nils
AU - Weinstein, John N.
AU - Weisenberger, Daniel J.
AU - Wilkerson, Matthew D.
AU - Wise, Lisa
AU - Witte, John
AU - Wu, Chia Chin
AU - Wu, Junyuan
AU - Wu, Ye
AU - Xu, Andrew W.
AU - Yadav, Shalini S.
AU - Yang, Liming
AU - Yang, Lixing
AU - Yau, Christina
AU - Ye, Huihui
AU - Yena, Peggy
AU - Zeng, Thomas
AU - Zenklusen, Jean C.
AU - Zhang, Hailei
AU - Zhang, Jianhua
AU - Zhang, Jiashan
AU - Zhang, Wei
AU - Zhong, Yi
AU - Zhu, Kelsey
AU - Zmuda, Erik
N1 - Publisher Copyright: © 2015 Elsevier Inc.
PY - 2015/11/5
Y1 - 2015/11/5
N2 - Summary 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.
AB - Summary 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.
UR - http://www.scopus.com/inward/record.url?scp=84946195510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946195510&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2015.10.025
DO - 10.1016/j.cell.2015.10.025
M3 - Article
C2 - 26544944
AN - SCOPUS:84946195510
SN - 0092-8674
VL - 163
SP - 1011
EP - 1025
JO - Cell
JF - Cell
IS - 4
ER -