Identification of Germinal Mutations in Eight Exons of the BRCA1 Gene in Breast Cancer Patients in the State of Amazonas, Using Direct Sequencing

Mutations in the BRCA1 gene are responsible for 50% of cases of hereditary breast cancer. The objective of this study was to perform screening of mutations in the BRCA1 gene in breast cancer patients treated in the state of Amazonas, Brazil. We analyzed 53 patients (51 women and 2 men) ranging from 30 to 71 years of age. Most of these patients were born in the state of Amazonas,and had a family history for predisposition to cancer and evidenced hormonal risk factor. The alterations found in the exons of the gene that were studied were verified in three online databases for this gene (ClinVar, BRCA Exchange and Varsome). A total of four mutations were identified: missense mutation c.4304T > C exon 13 (16 patients), missense mutation c.4837A > G exon 16 (25 patients), frameshift mutation c.5266dupC exon 20 (1 patient) and intronic mutation c.5277+48_5277+59dup (1 patient). Of the 53 patients studied, 26 were carriers of mutations, and only one patient presented the Ashkenazi founder mutation c.5266dupC; a mutation already identified in genetic studies in the Brazilian population. The mutation c.4837A>G occurred in 25 patients ruling out the possibility of being deleterious. Two of the mutations reported in this study do not yet have data on their molecular mechanisms in the literature, and thus demand further study in order to obtain a better understanding of the role of these mutations in the BRCA1 gene in the Brazilian population, as well as for the rest of world.