De novo recurrent germline mutation of the BRCA2 gene in a patient with early onset breast cancer

Germline mutations in either of the two major breast cancer predisposition genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast/ovarian cancer. Identification of breast cancer patients carrying mu tations of these genes is primarily based on a positive family history of b reast/ovarian cancer or early onset of the disease or both. In the course o f mutation screening of the BRCA1 and BRCA2 genes in a hospital based serie s of patients with risk factors for hereditary breast/ovarian cancer, we id entified a germline mutation in the BRCA2 gene (3034del4) in a patient with early onset breast cancer and no strong family history of the disease. Sub sequent molecular analysis in her parents showed that neither of them carri ed the mutation. Paternity was confirmed using a set of highly polymorphic markers, showing that the proband carried a de novo germline mutation in th e BRCA2 gene. Interestingly, 3034del4 is a recurrent mutation occurring in a putative mutation prone region of the BRCA2 gene. Our study presents the first case in which a de novo germline mutation in the BRCA2 gene has been identified, and supports previous results of haplotype studies, confirming that the 3034del4 mutation has multiple independent origins.