Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry

// Gabriela C. Fernandes 1, * , Rodrigo A.D. Michelli 2, * , Henrique C.R. Galvão 2, * , André E. Paula 1 , Rui Pereira 3, 4 , Carlos E. Andrade 2 , Paula S. Felicio 5 , Cristiano P. Souza 2 , Deise R.P. Mendes 1 , Sahlua Volc 2 , Gustavo N. Berardinelli 1 , Rebeca S. Grasel 2 , Cristina S. Sabato 1 , Danilo V. Viana 2 , José Carlos Machado 4 , José Luis Costa 4, Edmundo C. Mauad 2, 6 , Cristovam Scapulatempo-Neto 1, 5, 7 , Banu Arun 8 , Rui M. Reis 1, 2, 5, 9, 10 , Edenir I. Palmero 1, 2, 5, 11 1 Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil 2 Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil 3 Institute of Research and Innovation in Health, University of Porto, Porto, Portugal 4 Institute of Molecular Pathology and Immunology at the University of Porto (IPATIMUP), Porto, Portugal 5 Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil 6 Prevention Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil 7 Pathology Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil 8 MD Anderson Cancer Center, Houston, Texas, USA 9 Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal 10 ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimarães, Portugal 11 Barretos School of Health Sciences, Dr. Paulo Prata–FACISB, São Paulo, Brazil * These authors contributed equally to this work Correspondence to: Edenir I. Palmero, email: edenirip@yahoo.com.br Keywords: hereditary breast cancer, BRCA1/BRCA2 mutation profile in Brazil, genetic ancestry, HBOC in brazil, c.5266dupC prevalence in brazil Received: April 04, 2016      Accepted: October 01, 2016      Published: October 12, 2016 ABSTRACT Background: There are very few data about the mutational profile of families at-risk for hereditary breast and ovarian cancer (HBOC) from Latin America (LA) and especially from Brazil, the largest and most populated country in LA. Results: Of the 349 probands analyzed, 21.5% were BRCA1/BRCA2 mutated, 65.3% at BRCA1 and 34.7% at BRCA2 gene. The mutation c.5266dupC (former 5382insC) was the most frequent alteration, representing 36.7% of the BRCA1 mutations and 24.0% of all mutations identified. Together with the BRCA1 c.3331_3334delCAAG mutation, these mutations constitutes about 35% of the identified mutations and more than 50% of the BRCA1 pathogenic mutations. Interestingly, six new mutations were identified. Additionally, 39 out of the 44 pathogenic mutations identified were not previously reported in the Brazilian population. Besides, 36 different variants of unknown significance (VUS) were identified. Regarding ancestry, average ancestry proportions were 70.6% European, 14.5% African, 8.0% Native American and 6.8% East Asian. Materials and methods: This study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry. Conclusions: This is the largest report of BRCA1/BRCA2 assessment in an at-risk HBOC Brazilian population. We identified 21.5% of patients harboring BRCA1/BRCA2 mutations and characterized the genetic ancestry of a sample group at-risk for hereditary breast cancer showing once again how admixed is the Brazilian population. No association was found between genetic ancestry and mutational status. The knowledge of the mutational profile in a population can contribute to the definition of more cost-effective strategies for the identification of HBOC families.