Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer

Nat Commun. 2014 Sep 25;5:4988. doi: 10.1038/ncomms5988.

Abstract

A hypermutated subtype of advanced prostate cancer was recently described, but prevalence and mechanisms have not been well-characterized. Here we find that 12% (7 of 60) of advanced prostate cancers are hypermutated, and that all hypermutated cancers have mismatch repair gene mutations and microsatellite instability (MSI). Mutations are frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1 epigenetic silencing. Our findings identify parallels and differences in the mechanisms of hypermutation in prostate cancer compared with other MSI-associated cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mismatch Repair
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • MutS Homolog 2 Protein / genetics*
  • MutS Homolog 2 Protein / metabolism
  • Mutation*
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics*
  • Protein Binding

Substances

  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MSH2 protein, human
  • MutS Homolog 2 Protein

Associated data

  • SRA/SRP044943