Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Academic Article uri icon

Overview

MeSH

  • Exome
  • Humans
  • Male
  • Sequence Analysis, DNA

MeSH Major

  • Hepatocyte Nuclear Factor 3-alpha
  • Mediator Complex
  • Microtubule-Associated Proteins
  • Mutation
  • Prostatic Neoplasms

abstract

  • Prostate cancer is the second most common cancer in men worldwide and causes over 250,000 deaths each year. Overtreatment of indolent disease also results in significant morbidity. Common genetic alterations in prostate cancer include losses of NKX3.1 (8p21) and PTEN (10q23), gains of AR (the androgen receptor gene) and fusion of ETS family transcription factor genes with androgen-responsive promoters. Recurrent somatic base-pair substitutions are believed to be less contributory in prostate tumorigenesis but have not been systematically analyzed in large cohorts. Here, we sequenced the exomes of 112 prostate tumor and normal tissue pairs. New recurrent mutations were identified in multiple genes, including MED12 and FOXA1. SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6-15% of tumors across multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family gene rearrangements and showed a distinct pattern of genomic alterations. Thus, SPOP mutations may define a new molecular subtype of prostate cancer.

authors

publication date

  • May 20, 2012

has subject area

  • Exome
  • Hepatocyte Nuclear Factor 3-alpha
  • Humans
  • Male
  • Mediator Complex
  • Microtubule-Associated Proteins
  • Mutation
  • Prostatic Neoplasms
  • Sequence Analysis, DNA

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3673022

Digital Object Identifier (DOI)

  • 10.1038/ng.2279

PubMed ID

  • 22610119

Additional Document Info

start page

  • 685

end page

  • 689

volume

  • 44

number

  • 6