Mutational analysis of BRCA2 in Spanish breast cancer patients from Castilla-Leon: identification of four novel truncating mutations.

Mutations in BRCA1 and BRCA2 account for approximately 5% of the overall familial risk of breast cancer. We have carried out a mutational analysis of the entire coding sequence of the BRCA2 gene in 150 breast cancer patients from Castilla-Leon by two different methods: Protein Truncation Test (PTT) and Conformation-Sensitive Gel Electrophoresis (CSGE). We have identified 10 distinct truncating mutations of the BRCA2 protein in 17 unrelated patients. Four mutations had not been previously described in any other population: two nonsense, Q2354X and K3083X, and two frameshift deletions, 6126delT and 5374delTATG. Moreover, three further mutations, 1538delAAGA, E1308X and S2219X, had not been reported in Spanish patients until now. Five mutations were recurrent: 3036delACAA, 1538delAAGA, 9538delAA and the novel mutations, 6126delT and 5374delTATG. The most prevalent mutation was 3036delACAA found in four unrelated patients.