The Molecular Taxonomy of Primary Prostate Cancer. Academic Article uri icon

Overview

MeSH

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

MeSH Major

  • Prostatic Neoplasms

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. Copyright © 2015 Elsevier Inc. All rights reserved.

authors

publication date

  • November 5, 2015

has subject area

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

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4695400

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2015.10.025

PubMed ID

  • 26544944

Additional Document Info

start page

  • 1011

end page

  • 1025

volume

  • 163

number

  • 4