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

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.

摘要 与乳腺癌发生相关的特异性致病突变可因种族群体而异。以BRCA1 c.5266dupC突变为例，该突变最初被认定为德系犹太人群体中的奠基者突变（founder mutation），后续亦在其他人群中被检出。在巴西人群中，该突变占已报道的致病性BRCA1变异的20%。本研究旨在探究携带BRCA1基因c.5266dupC突变的巴西家族队列的单倍型（haplotype）组成，并验证欧洲、非洲及美洲原住民来源的祖先遗传贡献。研究共纳入14名携带c.5266dupC突变的先证者（probands）以及16名亲属（含突变携带者与非携带者）开展分析。所有受检家族均显示突变与相同单倍型共分离，在0.68 Mb的基因组区域内未检测到重组事件。祖先起源分析结果显示，先证者的遗传组分以欧洲来源为主。针对BRCA1 c.5266dupC突变的分析表明，巴西人群中存在该突变的奠基者效应（founder effect）。