Germline RAD51B truncating mutation in a family with cutaneous melanoma

TY - JOUR

T1 - Germline RAD51B truncating mutation in a family with cutaneous melanoma

AU - Wadt, Karin A W

AU - Aoude, Lauren G

AU - Golmard, Lisa

AU - Hansen, Thomas V O

AU - Sastre-Garau, Xavier

AU - Hayward, Nicholas K

AU - Gerdes, Anne-Marie

PY - 2015/6/28

Y1 - 2015/6/28

N2 - 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.

AB - 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.

KW - DNA-Binding Proteins

KW - Germ-Line Mutation

KW - Humans

KW - Immunohistochemistry

KW - Melanoma

KW - Middle Aged

KW - Skin Neoplasms

U2 - 10.1007/s10689-015-9781-4

DO - 10.1007/s10689-015-9781-4

M3 - Journal article

C2 - 25600502

SN - 1389-9600

VL - 14

SP - 337

EP - 340

JO - Familial Cancer

JF - Familial Cancer

IS - 2

ER -