Mutation screening of TP53, CHEK2 and BRCA genes in patients at high risk for hereditary breast and ovarian cancer (HBOC) in Brazil

Background Few studies related to hereditary breast and ovarian cancer syndrome (HBOC) have been conducted in Brazil, and they are restricted to only small areas of the country. Here, we report the mutation profile of BRCA1 / 2, CHEK2 and TP53 genes in a cohort from Minas Gerais state. Methods These genes from 44 patients at high risk for HBOC were screened through high-resolution melting and/or sequencing. The pathogenicity of the alterations was checked using ClinVar database and bioinformatics programs. Results In BRCA genes we identified 46 variants, 38 without clinical significance and 8 pathogenic mutations including a new pathogenic mutation in BRCA1 gene (c.4688_4694delACCTGGAinsG). The most prevalent pathogenic mutation was c.4829_4830delTG, in the BRCA2 gene. This mutation was not described in the Brazilian population up to now and in this study, it was described with a prevalence of 6.8%. The p.R337H mutation in TP53 gene was found in one patient clinically diagnosed as HBOC and without clinical criteria for Li-Fraumeni syndrome. In CHEK2 gene, the undescribed variant c.485A > G was found and it presents as probably pathogenic through in silico analyses. Pathogenic mutations were found in 29.5% of the patients, 11.3% in BRCA1 , 15.9% in BRCA2 and 2.3% in TP53 gene. Conclusions Brazilian population is one of the most heterogeneous in the world and the mutational profile knowledge of genes related to HBOC from different regions can contribute to the definition of more cost-effective strategies for the prevention, identification and treatment of cancer.