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Analysis of RAD51C germline mutations in high‐risk breast and ovarian cancer families and ovarian cancer patients
Author(s) -
Thompson Ella R.,
Boyle Samantha E.,
Johnson Julie,
Ryland Georgina L.,
Sawyer Sarah,
Choong David Y.H.,
ChenevixTrench Georgia,
Trainer Alison H.,
Lindeman Geoffrey J.,
Mitchell Gillian,
James Paul A.,
Campbell Ian G.
Publication year - 2012
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21625
Subject(s) - ovarian cancer , breast cancer , germline mutation , penetrance , biology , missense mutation , oncology , germline , family history , genetic testing , cancer , mutation , medicine , cancer research , genetics , phenotype , gene
There is strong evidence that overtly inactivating mutations in RAD51C predispose to hereditary breast and ovarian cancer but the prevalence of such mutations, and whether they are associated with a particular clinical phenotype, remains unclear. Resolving these questions has important implications for the implementation of RAD51C into routine clinical genetic testing. Consequently, we have performed a large RAD51C mutation screen of hereditary breast and ovarian cancer families, and the first study of unselected patients diagnosed with ovarian cancer. Our data confirm a consistent but low frequency (2/335 families) of inactivating RAD51C mutations among families with a history of both breast and ovarian cancer and an absence of mutations among breast cancer only families (0/1,053 families). Our data also provide support for the designation of the missense variant p.Gly264Ser as a moderate penetrance allele. Hum Mutat 33:95–99, 2012. © 2011 Wiley Periodicals, Inc.