Produção Nacional
Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry
2016; Impact Journals LLC; Volume: 7; Issue: 49 Linguagem: Inglês
10.18632/oncotarget.12610
ISSN1949-2553
AutoresGabriela Carvalho Fernandes, Rodrigo Augusto Depieri Michelli, Henrique C.R. Galvão, André Escremim de Paula, Rui Pereira, Carlos Eduardo Mattos Cunha Andrade, Paula Silva Felicio, Cristiano de Pádua Souza, Deise R.P. Mendes, Sáhlua Miguel Volc, Gustavo Nóriz Berardinelli, Rebeca Silveira Grasel, Cristina S. Sabato, Danilo Vilela Viana, José Carlos Machado, José Luís Costa, Edmundo Carvalho Mauad, Cristovam Scapulatempo‐Neto, Banu K. Arun, Rui Manuel Reis, Edenir Inêz Palmero,
Tópico(s)Genomic variations and chromosomal abnormalities
ResumoThere 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.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.This study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry.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.
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