BRCA1mutation analysis in breast and ovarian cancer families from Greece

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We have been constructing a genomic DNA database from breast/ovarian cancer patients with a family history, in collaboration with several Greek hospitals. The criteria used for the selection of high-risk families are those accepted universally. In the present study we report three frameshift mutations in BRCA1. These mutations were found in female patients with a family history of breast/ovarian cancer, and are all located in exon 11. Mutation identification was made using PTT and direct sequencing. The first mutation identified is 3741insA (codon 1208), carried by a woman who developed bilateral breast cancer at age 31 with her mother's sister affected with breast cancer at age 35. This mutation is reported only once in the BIC database. The second case is a woman with ovarian cancer carrying the mutation 1623del5-TTAAA (codon 502). Her daughter developed breast cancer and her mother endometrial cancer. This mutation has been reported 6 times in the BIC database. The third BRCA1 mutation, 3099delT (codon 994) is a novel mutation and was found in a woman with ovarian cancer at age 33, with her sister and mother affected with ovarian cancer at different ages. Her grandmother was also affected with breast and ovarian cancer. We have also screened breast/ovarian patients with a family history for two mutations with strong founder effects, 22 patients for 185delAG and 26 patients for 5382insC. None of these mutations was found, indicating that their frequency in Greece might be quite different from those reported by Olah et al [1] concerning Central and Eastern Europe. Mutation analysis of more breast/ovarian patients is in progress. This is the first report of BRCA1 deleterious mutations identified in Greece.