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The Molecular Taxonomy of Primary Prostate Cancer

Journal article published in 2015 by 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 and other authors.
This paper is available in a repository.
This paper is available in a repository.

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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. ; National Institutes of Health (U.S.). (grant 5U24CA143799) ; National Institutes of Health (U.S.). (grant 5U24CA143835) ; National Institutes of Health (U.S.). (grant 5U24CA143840) ; National Institutes of Health (U.S.). (grant 5U24CA143843) ; National Institutes of Health (U.S.). (grant 5U24CA143845) ; National Institutes of Health (U.S.). (grant 5U24CA143848) ; National Institutes of Health (U.S.). (grant 5U24CA143858) ; National Institutes of Health (U.S.). (grant 5U24CA143866) ; National Institutes of Health (U.S.). (grant 5U24CA143867) ; National Institutes of Health (U.S.). (grant 5U24CA143882) ; National Institutes of Health (U.S.). (grant 5U24CA143883) ; National Institutes of Health (U.S.). (grant 5U24CA144025) ; National Institutes of Health (U.S.). (grant U54HG003067) ; National Institutes of Health (U.S.). (grant U54HG003079) ; National Institutes of Health (U.S.). (grant U54HG003273) ; National Institutes of Health (U.S.). (grant P30CA16672)