Gene Expression Profiles Of Ghanaian And Ethiopian Triple-Negative Breast Tumors

Background: Triple-negative breast cancer (TNBC) remains the most aggressive molecular subtype of breast cancer, with worse survival outcomes compared to other breast cancer subtypes. TNBC prevalence is highest among women of African descent worldwide, and through our previous work we have established a connection between West African ancestry (WAa) and higher rates of TNBC. Specifically, we have shown that prevalence rates of TNBC among West African and African American women are similar and higher than that of East African and White American women. We have also shown that quantified African ancestry is higher among TNBC cases compared to non-TNBC cases. To determine the influence African ancestry on the TNBC tumor environment, we sought to determine any differences in gene expression profiles of Ghanaian (West African) compared to Ethiopian (East African) women. Methods: RNA was extracted and sequenced from a pilot cohort of archival FFPE tumor tissue among Ghanaian (n = 19) and Ethiopian (n = 20) women. RNAseq reads were aligned, and quality of alignments were assessed, where de-duplicated samples with counts above 10M reads were included in the final analysis. Genetic ancestry was quantified by obtaining SNVs called from the RNAseq alignments, using GATK best practices. Differentially expressed genes lists were determined comparing Ghanaian vs. Ethiopian TNBC tumors, and also by identifying genes that were associated with increasing African ancestry. These gene lists, and log-fold change between comparison groups, were used as input for Ingenuity Pathway Analysis (IPA), to identify canonical pathways and de novo networks that are specific to Ghanaian or Ethiopian TNBC tumors. Results: Using 1KG populations as our reference to quantify genetic ancestry, we show that Ghanaian samples have >94% AFR ancestry, specifically matching population groups representative of WAa. The Ethiopian samples showed between 37-48% AFR ancestry, primarily represented by East African groups. Interestingly, there seems to be a significant proportion of EUR ancestry among the Ethiopians samples (30-49%), primarily represented by Italian ancestry. We have conducted the differential gene expression analysis in two ways. First, we have compared gene expression profiles between Ghanaian and Ethiopian tumors. In our preliminary analysis, we identified >600 genes (p 900 genes associated with AFR ancestry (p Citation Format: Rachel Martini, Endale Gebregzabher, Princesca Dorsaint, Timothy Chu, Kanika Arora, Lee Gibbs, Zarko Manojlovic, Nicolas Robine, Andrea Sboner, Olivier Elemento, John Carpten, Lisa Newman, Melissa Davis. Gene expression profiles of Ghanaian and Ethiopian triple-negative breast tumors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS1-07.