Abstract 1292: Identification of BRCA1 and BRCA2 founder mutations in population isolates from Colombia

Abstract

Abstract Breast cancer (BC) is the most common malignancy in women. Germline mutations in breast cancer risk genes, such as BRCA1 and BRCA2, account for a large portion of hereditary breast cancer families. The contribution of mutations in breast cancer susceptibility genes has been poorly investigated in minority populations, such as in Hispanics from South America. While mutations in BRCA1 and BRCA2 display a heterogeneous mutation spectrum, specific mutations often occur in population isolates. Using the KASP genotyping technology, we screened 476 unselected Colombian breast cancer patients for three common BRCA1 and one BRCA2 founder mutations in the Hispanic population. The BRCA2 c.2806_2809delAAAC founder mutation was identified in 3 of the 476 BC cases (0.6%). Strikingly, 24 out of 476 cases (5.0%) harbored the BRCA1 founder mutation c.3331_3334delCAAG, which has also been reported in Southern European populations, including Spain and Portugal. The clinical data and family history of these patients have highlighted a distinct geographic region from where these cases originate. This finding potentially represents one of the most remarkable founder effects reported in human populations. To date the arrival of the BRCA1 c.3331_3334delCAAG mutation to Colombia, we are completing haplotype analysis of the patients and their families, along with BC cases from Spain and Portugal that harbor the same mutation. Interestingly, haplotype analyses of our BC cases have revealed a haplotype larger than 3.5 cM. In the future, we aim to perform haplotype analysis of family members of the mutation carriers and BC cases from Portugal and Spain to further study the haplotype around this BRCA1 mutation, which will allow us to date the origin of the mutation. By understanding the prevalence of mutations in known breast cancer risk genes in minority populations, cancer disparities can be better addressed and breast cancer screening can be improved. Furthermore, the ability to identify such strong founder effects highlights an advantage of using this Colombian population isolate in facilitating the identification of novel BC risk genes. Citation Format: Anna Marie D. Tuazon, Carolina Ramírez, Mabel Bohorquez, Rodrigo Prieto, Jorge Castro, Gilbert Mateus, Alejandro Velez, Magdalena Echeverry, Luis G. Carvajal-Carmona. Identification of BRCA1 and BRCA2 founder mutations in population isolates from Colombia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1292. doi:10.1158/1538-7445.AM2014-1292