The Molecular Taxonomy of Primary Prostate Cancer.

Cancer Genome Atlas Research Network
Cell. 2015 163 (4): 1011-25

PMID: 26544944 · PMCID: PMC4695400 · DOI:10.1016/j.cell.2015.10.025

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.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (13)

DNA Repair Epigenesis, Genetic Gene Expression Regulation, Neoplastic Gene Fusion Humans Male Mutation Neoplasm Metastasis Phosphatidylinositol 3-Kinases Prostatic Neoplasms ras Proteins Receptors, Androgen Signal Transduction

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