The Molecular Taxonomy of Primary Prostate Cancer

Anuradha Gopalan , Markus Graefen , Kiley Graim , Anuradha Gopalan , Markus Graefen , Kiley Graim , Thomas Gribbin , Ranabir Guin , Manaswi Gupta , Angela Hadjipanayis , Syed Haider , Lucie Hamel , D. Neil Hayes , David I. Heiman , 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
2015 Cell 3,105 citations

Abstract

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.

Keywords

BiologyPrimary (astronomy)Prostate cancerTaxonomy (biology)Computational biologyCancerMolecular taxonomyProstateGeneticsEcologyGenePhylogenetics

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Year
2015
Type
article
Volume
163
Issue
4
Pages
1011-1025
Citations
3105
Access
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Anuradha Gopalan, Markus Graefen, Kiley Graim et al. (2015). The Molecular Taxonomy of Primary Prostate Cancer. Cell , 163 (4) , 1011-1025. https://doi.org/10.1016/j.cell.2015.10.025

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DOI
10.1016/j.cell.2015.10.025