Background and objective: The objective of the present study was to investigate the mutational spectrum of BRCA1 and BRCA2 in the Valencian Community, comparing this spectrum with that reported in Spain. We also analyze the association of the mutations with the family history of the selected families.
Patients and method: We analyzed the mutations in the BRCA1 and BRCA2 in 147 families with history of breast and/or ovarian cancer. The detection was based on the amplification of in frame and flanking regions of BRCA1 and BRCA2 genes by polymerase chain reaction, detection of the heteroduplex formed by conformation-sensitive gel electrophoresis and their characterization by sequencing.
Results: We identified 24 different pathogenic mutations in 50 out of the 147 families (34.0%; 23 in BRCA1 and 27 in BRCA2). The higher incidence of pathogenic mutations was observed in families with breast and ovarian cancer or with more than 3 cases of breast cancer. The most frequent mutations in BRCA1 were the c.187_188delAG, c.2080delA and the c.3889_3890delAG, whereas for BRCA2 the mutations with higher prevalence was observed for c.9254_9258delATCAT and the c.9204delCATCAGATTTATAT. We detected 5 pathogenic mutations (p.Y1429X in BRCA1 and c.1835insT, c.5025delT, c.6722delT and p.Q3156X in BRCA2) not reported in the Breast Cancer Information Core Database. Among them, the BRCA2 mutations c.1835insT and c.5025delT were recurrent and seemed to be characteristic of the population the Valencian Community.
Conclusions: We detected pathogenic mutations in BRCA1 and BRCA2 genes in 34.0% of the families studied. The mutations c.1835insT and c.5025delT were 2 new recurrent pathogenic mutations in BRCA2 that seemed to be characteristic of the population of the Valencian Community. The study reports 5 new pathogenic mutations to the world spectrum of BRCA1 and BRCA2 mutations and other 5 mutations to the Spanish spectrum.