Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American and European American women. RNA sequencing data was analyzed to measure changes in genome-wide expression, and we utilized logistic regressions to identify ancestry-associated gene expression signatures. Using SNVs identified from our RNA sequencing data, global ancestry was estimated. We identified 156 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like 2 tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated. We created a novel tool to determine the heterogenic status of TNBC, which accounts for proportional differences multiple cell 'subtypes'.

Citation Format: Melissa B. Davis, Rachel Martini, Lisa A. Newman, Olivier Elemento, Jason White, Akanksha Verma, Indrani Datta, Indra Adrianto, Yalei Chen, Kevin Gardner, Hyung-Gyoon Kim, Windy D. Coleman, Isam-Eldin Eltoum, Andra Frost, William Grizzle, Andrea Sboner, Upender Manne, Clayton Yates. Distinct heterogeneous subtypes of Triple-Negative Breast Cancer, associated with African Ancestry [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA34.