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. 2012 Apr 10;106(8):1460-3.
doi: 10.1038/bjc.2012.87. Epub 2012 Mar 13.

Mutation analysis of RAD51D in non-BRCA1/2 ovarian and breast cancer families

D J Osher  1 , K De Leeneer, G Michils, N Hamel, E Tomiak, B Poppe, K Leunen, E Legius, A Shuen, E Smith, J Arseneau, P Tonin, G Matthijs, K Claes, M D Tischkowitz, W D Foulkes
Affiliations

Mutation analysis of RAD51D in non-BRCA1/2 ovarian and breast cancer families

D J Osher et al. Br J Cancer. .

Abstract

Background: Recent data show that mutations in RAD51D have an aetiological role in ovarian carcinoma, yet mutations do not appear to be associated with an increased risk for breast cancer. We studied ovarian and breast cancer families having at least one woman affected by ovarian carcinoma, to assess the importance of RAD51D mutations in such families.

Methods: The coding region of the RAD51D gene was analysed in 175 BRCA1/2-negative families with family histories of both ovarian and breast cancer ascertained from two Canadian and two Belgian institutions.

Results: We identified one previously reported deleterious mutation, p.Arg186(*) (c.556C>T), and two novel variants; missense substitution p.Cys119Arg and an intronic variant c.83-26A>G. p.Arg186(*) segregated with the disease in the family and two ovarian carcinomas available for analysis showed loss of the wild-type allele, but the novel variants are likely neutral.

Conclusion: RAD51D should be included in genetic screening of ovarian cancer families that do not have BRCA1/BRCA2 mutations. We show that mutations are more likely to be found in families with two or more ovarian cancers, or in probands with first-degree relatives with ovarian cancer, and we feel testing should be preferentially offered to affected women from such families.

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Figures

Figure 1
Figure 1
(A) Pedigree of family from Montreal, carrying the deleterious mutation p.Arg186* (c.556C>T) in RAD51D. Individual II:2 had clear cell ovarian carcinoma, and II:11 had high-grade, serous ovarian carcinoma. (B) Sequencing results from individual II:2 showing the heterozygous mutation in germline DNA and loss of the wild-type allele in DNA extracted from the patient's ovarian tumour as compared with wild-type control DNA. Germline DNA was obtained from lymphocytes. (C) Sequencing results from individual II:11 showing a heterozygous mutation in normal DNA and loss of the wild-type allele in DNA extracted from the patient's ovarian tumour, compared with wild-type control DNA. Normal DNA was extracted from macro-dissected normal tissue from the patient's ovarian FFPE tumour block. Abbreviations: BC=breast cancer; DCIS=ductal carcinoma in situ; OC=ovarian cancer; PrC=prostate cancer.
See this image and copyright information in PMC

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