Journal article

The Molecular Taxonomy of Primary Prostate Cancer

Adam Abeshouse, Jaeil Ahn, Rehan Akbani, Adrian Ally, Samirkumar Amin, Christopher D 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 Berrios, Adrian Bivol Show all

Cell | CELL PRESS | Published : 2015

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 tum..

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Awarded by NIH


Funding Acknowledgements

We are grateful to all the affected individuals and families who contributed to this study. We thank Margi Sheth and Ina Felau for project management. This work was supported by the following grants from the NIH: 5U24CA143799, 5U24CA143835, 5U24CA143840, 5U24CA143843, 5U24CA143845, 5U24CA143848, 5U24CA143858, 5U24CA143866, 5U24CA143867, 5U24CA143882, 5U24CA143883, 5U24CA144025, U54HG003067, U54HG003079, U54HG003273, and P30CA16672. D.J.W. is a consultant for Zymo Research Corporation. S.A.T., M.A.R., and F.D. are coauthors on a patent issued to the University of Michigan and the Brigham and Women's Hospital regarding ETS gene fusions in prostate cancer. The diagnostic field of use has been licensed to Hologic/Gen-Probe, Inc., who has sub-licensed some rights to Ventana Medical Systems. S.A.T. is a coauthor on a patent filed by the University of Michigan regarding SPINK1 in prostate cancer. The diagnostic field of use has been licensed to Hologic/Gen-Probe, Inc., who has sub-licensed some rights to Ventana Medical Systems. S.A.T. has served as a consultant and received honoraria from Ventana Medical Systems. M.A.R. is a co-inventor of the patent for the detection and therapeutic field of SPOP mutations in prostate cancer filed by Cornell University. E.V.A. is a consultant for Syapse and Ventana Medical Systems and owns equity in Syapse and Microsoft. A.D.C. has received research support from Bayer, AG. M.B.G. serves on the SAB of BINA. R. Beroukhim is a consultant for and received grant funding from Novartis. M. Meyerson received research support from Bayer and has equity in and is a consultant for Foundation Medicine.