African Ancestry Associated Gene Expression Profiles in Triple Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent

Women of sub-Saharan African descent have disproportionately higher incidence of Triple Negative Breast Cancer (TNBC), and TNBC-specific mortality. Population comparative studies show racial differences in TNBC biology, including higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily United States (US) populations. Due to heterogenous genetic admixture, and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed tumor-associated immunological profiles are distinct in patients of African descent. Overall design: Determination of African-ancestry associated gene signatures in Triple Negative Breast Cancer using a RNAseq cohort of women of African descent, including Ghanaian, Ethiopian and African American women