title: Germline RAD51B truncating mutation in a family with cutaneous melanoma.
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.
authors.affiliation: Department of Clinical Genetics, Rigshospitalet, 4062, Blegdamsvej 9, 2100, Copenhagen, Denmark, Karin.wadt@rh.regionh.dk.
authors.forename: Karin A W
authors.initials: KA
authors.lastname: Wadt
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Aoude
authors.forename: Lisa
authors.initials: L
authors.lastname: Golmard
authors.forename: Thomas V O
authors.initials: TV
authors.lastname: Hansen
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Gerdes
mesh_terms: D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C413002:RAD51B protein, human