Haplotypic characterization of BRCA1 c.5266dupC, the prevailing mutation in Brazilian hereditary breast/ovarian cancer.

Renan Gomes,Patrícia Ashton-Prolla,Rodrigo Michelli,Barbara Alemar,Cristina B O Netto,Edenir Inêz Palmero,Barbara Luisa Soares,Paula Silva Felicio,Miguel Ângelo Martins Moreira

doi:10.1590//1678-4685-gmb-2019-0072

Abstract

Specific pathogenic mutations associated with breast cancer development can vary between ethnical groups. One example is BRCA1 c.5266dupC that was first described as a founder mutation in the Ashkenazi Jewish population, but was later also found in other populations. In Brazil, this mutation corresponds to 20% of pathogenic BRCA1 variants reported. Our objective was to investigate the haplotype component of a group of Brazilian families who inherited c.5266dupC in the BRCA1 gene and to verify the ancestry contribution from European, African, and Amerindian origins. Fourteen probands carrying c.5266dupC and 16 relatives (carriers and non-carriers) were investigated. The same haplotype was observed segregating within all the families analyzed, revealing no recombinants in a region of 0.68 Mb. Ancestry analysis demonstrated that the European component was predominant among probands. The BRCA1 c.5266dupC analysis indicates that there was a founder effect in the Brazilian population.

Highlights

The spectrum of pathogenic mutations found in genes related to cancer development can vary depending on the ethnic groups that are being studied
E-mail: miguelm@inca.gov.br. (OMIM #600185): BRCA1c.66_67delAG (p.Glu23fs), BRCA1 c.5266dupC (p.Gln1756fs, former named 5382insC), and BRCA2c.5946delT (p.Ser1982fs) (Rubinstein, 2004; Antoniou et al, 2005; Ferla et al, 2007; Hamel et al, 2011; Tafe et al, 2015). These pathogenic mutations were first identified in Ashkenazi Jews, BRCA1 c.5266dupC, was later described in other populations. It has already been identified in many countries of Central and Eastern Europe (Burcos et al, 2013; Gorodetska et al, 2015) and recurrently described in the Brazilian population (Lourenço et al, 2004; da Costa et al, 2008; Fernandes et al, 2016), representing 20% of the BRCA1 pathogenic variants reported in a recent survey (Palmero et al, 2018)
Data available in Brazil regarding the frequency of different pathogenic variants in individuals at risk of hereditary breast/ovary cancer and the availability of samples from the c.5266dupC mutation carriers limited the conclusions at that time with respect to a possible founder effect

Summary

Short Communication Human and Medical Genetics

Haplotypic characterization of BRCA1 c.5266dupC, the prevailing mutation in Brazilian hereditary breast/ovarian cancer. Barbara Alemar4,5 , Patrícia Ashton-Prolla4,5 , Edenir Inêz Palmero and Miguel Ângelo Martins Moreira

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Findings

Author Contributions