The germline mutational landscape of BRCA1 and BRCA2 in Brazil.
Edenir Inez PalmeroDirce Maria CarraroBárbara AlemarMiguel Angelo Martins MoreiraÂndrea Kely Campos Ribeiro Dos SantosKiyoko Abe-SandesHenrique Campos Reis GalvãoRui Manuel Vieira ReisCristiano de Pádua SouzaNatalia CampacciMaria Isabel AchatzRafael Canfield BrianeseMaria Nirvana da Cruz FormigaFabiana Baroni MakdissiFernando Regla VargasAnna Cláudia Evangelista Dos SantosHector N SeuanezKelly Rose Lobo de SouzaCristina B O NettoPatrícia Santos-SilvaGustavo Stumpf da SilvaRommel M R BurbanoSidney SantosPaulo Pimentel AssumpçãoIzabel Maria Monteiro BernardesTaisa Manuela Bonfim Machado-LopesThais Ferreira BomfimMaria Betânia Pereira TorallesIvana NascimentoBernardo GaricocheaSergio D SimonSimone NoronhaFernanda Teresa de LimaAnisse Marques ChamiCamila Matzenbacher BittarJose BinesOsvaldo ArtigalasMaria Del Pilar Esteves-DizTirzah Braz Petta LajusAna Carolina Leite Vieira Costa GifoniRodrigo S C GuindaliniTerezinha Sarquis CintraIda V D SchwartzPricila BernardiDiego MiguelSonia Tereza Dos Santos NogueiraJosef HerzogJeffrey N WeitzelPatricia Ashton-ProllaPublished in: Scientific reports (2018)
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 identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first 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 identified 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 effect. Our findings confirm that there is significant 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 first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.