The germline mutational landscape of BRCA1 and BRCA2 in Brazil

Abstract

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/ availability of genetic testing. Aiming at the identifcation of recurrent mutations that could be included in a low-cost mutation panel, used as a frst screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identifed in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder efect. Our fndings confrm that there is signifcant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the frst study to show that profles of recurrent mutations may be unique to diferent Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be efective.