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Germline RAD51C mutations in ovarian cancer susceptibility
Author(s) -
Coulet F,
Fajac A,
Colas C,
Eyries M,
DionMinière A,
Rouzier R,
Uzan S,
Lefranc JP,
Carbonnel M,
Cornelis F,
Cortez A,
Soubrier F
Publication year - 2013
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2012.01917.x
Subject(s) - fanconi anemia , palb2 , germline mutation , missense mutation , germline , genetics , ovarian cancer , biology , mutation , cancer research , sanger sequencing , gene , cancer , dna repair
Several genes might explain BRCA1 /2 negative breast and ovarian family cases. Deleterious mutations in few genes involved in the Fanconi complex are responsible for Fanconi anemia at the homozygous state and breast cancer ( BC ) susceptibility at the heterozygous state ( BRCA2 , PALB2 , BRIP1 ). RAD51C plays an important role in the double‐strand break repair pathway and a biallelic missense mutation in the RAD51C gene was found in a Fanconi anemia‐like disorder. Subsequently, six monoallelic pathogenic mutations were identified after screening 480 BRCA1 /2 negative breast and ovarian cancer ( BC/OC ) pedigrees. Several reports were unsuccessful to replicate these results. To investigate whether germline mutations in RAD51C are associated with an increased risk of developing BC/OC, we screened, by Sanger sequencing of the coding sequence, 117 index cases of breast and ovarian families from French or European origin, and negative for BRCA1 /2 mutations. In our study, we found 3 pathogenic mutations among 117 families screened which corresponds to a 2.6% frequency. Our results confirm that RAD51C is a susceptibility gene for ovarian and BC and that this gene should be screened for mutations in families with multiple BC/OC.