Germline RAD51B truncating mutation in a family with cutaneous melanoma

Fam Cancer. 2015 Jun;14(2):337-40. doi: 10.1007/s10689-015-9781-4.

Abstract

Known melanoma predisposition genes only account for around 40% of high-density melanoma families. Other rare mutations are likely to play a role in melanoma predisposition. RAD51B plays an important role in DNA repair through homologous recombination, and inactivation of RAD51B has been implicated in tumorigenesis. Thus RAD51B is a good candidate melanoma susceptibility gene, and previously, a germline splicing mutation in RAD51B has been identified in a family with early-onset breast cancer. In order to find genetic variants associated with melanoma predisposition, whole-exome sequencing was carried out on blood samples from a three-case cutaneous melanoma family. We identified a novel germline RAD51B nonsense mutation, and we demonstrate reduced expression of RAD51B in melanoma cells indicating inactivation of RAD51B. This is only the second report of a germline truncating RAD51B mutation. While this case report is consistent with melanoma being part of the RAD51B cancer spectrum further population-based screening of large case-control sample series will be needed to definitively establish if this is the case.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics*
  • Germ-Line Mutation*
  • Humans
  • Immunohistochemistry
  • Melanoma / genetics*
  • Middle Aged
  • Skin Neoplasms / genetics*

Substances

  • DNA-Binding Proteins
  • RAD51B protein, human