Abstract IA34: The impact of ancestry on mutational signatures in population with African ancestry

Abstract

Abstract Mutational processes generate variations in DNA that fuel tumor devolvement. These processes include DNA damage due to exposure to environmental carcinogens and DNA repair. Different processes may lead to varying rates and types of mutations in cancers. Mutational processes can be inferred from whole-exome sequencing data using a computational method called mutational signatures framework. Sequencing tumors across populations can reveal population-specific signatures that can be mapped to specific environmental exposures or genetics. Knowing how mutational processes lead to tumor formation is key to understating the etiology of cancer. We analyzed The Cancer Genome Atlas data and discovered a mutational signature characteristic of homologous recombination deficiency (HRD). We found that this HRD signature was mainly attributed to germline mutations in BRCA1/BRCA2 in whites and promoter methylation of BRCA1/RAD51C in patients of African ancestry. Patients with BRCA mutation will likely benefit from cisplatin inhibitors in both neoadjvant and at time of recurrence. Clinical trials suggest TNBC patients with methylation of BRCA1 are less likely to benefit from cisplatin at the time of recurrence. Hence our initial observation might indicate that black TNBC patients might benefit from other treatment strategies. Citation Format: Paz Polak. The impact of ancestry on mutational signatures in population with African ancestry [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA34.