Mutation analysis of RAD51D in non-BRCA1/2 ovarian and breast cancer families
| Autor: | Gert Matthijs, N Hamel, K De Leeneer, Eric Legius, Geneviève Michils, Jocelyne Arseneau, William D. Foulkes, Karin Leunen, Kathleen Claes, Eva Tomiak, Marc Tischkowitz, Patricia N. Tonin, Andrew Y Shuen, Bruce Poppe, Erika Smith, D J Osher |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
endocrine system diseases Short Communication DNA Mutational Analysis double-strand DNA repair Breast Neoplasms Biology medicine.disease_cause Sensitivity and Specificity Breast cancer Germline mutation Ovarian carcinoma medicine Missense mutation Humans Genetic Testing PARP inhibitors Genetic testing BRCA2 Protein Ovarian Neoplasms Mutation medicine.diagnostic_test RAD51C RAD51D BRCA1 Protein medicine.disease Pedigree ovarian carcinoma DNA-Binding Proteins Oncology Cancer research Female Ovarian cancer hereditary |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | 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.556C4T), and two novel variants; missense substitution p.Cys119Arg and an intronic variant c.83-26A4G. 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. |
| Databáze: | OpenAIRE |
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