Abstract 4023: Comparison of transcriptional signatures in US African American and Kenyan TNBC samples identifies differential expression in key oncogenic pathways.

Abstract

Abstract Strong epidemiological data supports breast cancer (BC) as the second leading cause of cancer death among US African American (AA) women, with a 20% greater mortality rate than that in Caucasians (Cauc). Collection of similar BC incidence and mortality data for Eastern Africa is limited, however, it is known that BC presents as advanced-stage disease, comprised mainly of poorly differentiated cancers that are less likely to be hormone responsive. Our combined investigative team continues to analyze a cohort of indigenous Kenyan BC patients, in order to begin to understand biological similarities and differences between BC in native African and AA patients. Previous related gene expression studies conducted in a Triple Negative Breast Cancer (TNBC) stage-matched multi-ethnic US cohort suggested differential expression patterns across ethnicities. We are extending this focus to similar studies involving native African samples. Archived BC pathology samples (FFPE) were either obtained from University of Miami or from a native African tumor bank (Kenya). Forty-seven BC samples were contributed from Kenya, and re-analyzed (in Miami) for ER/PR/ Her2Neu status, resulting in confirmation of 29 Kenyan TNBC cases. 10 um sections were cut from each tumor FFPE block, and following RNA isolation and cDNA preparation, hybridized to the Almac breast-enriched gene expression array (Breast Cancer DSA Research Tool). After quality control assessment of array data, a total of 60,856 gene/probes were analyzed by RMA; normalized, log transformed to the median, and compared on GeneSpring® analytical software. Data sets were separated by further analysis based on node status [(N0-Kenyan-7, AA-10); (Mixed Node-Kenyan-16, AA-7)]. Unpaired student's T-test was performed on all subsets and the resulting p-values were corrected for Multiple Testing using Benjamin-Hochberg. Differentially expressed genes/probes were extracted for each subset using p-value < 0.01 and fold change of > 1.5. These probe/gene lists were further analyzed using GeneGo pathway analysis and enriched pathways were identified. Comparisons of transcriptional differences between Kenyan and AA TNBC, regardless of node status, suggest expression alterations in several key pathways, including EMT Transition, Cytoskeleton Remodeling, Immune Response and Epigenetic Control. These preliminary results are being validated by QPCR and other methodologies. In conclusion, we have demonstrated that high quality RNA can be extracted from archived FFPE tumor samples, including samples from East Africa. This observation raises the possibility of future genomic analyses using archived samples. We are intrigued by our study observations, which suggest that inherent gene expression differences exist between Kenyan and AA TNBC samples in previously-recognized pathways important in onocogenesis. Citation Format: Lisa L. Baumbach-Reardon, Julie Getz, Mary Ellen Ahearn, Carmen Gomez, Peter Bird, John Carpten, Mark Pegram. Comparison of transcriptional signatures in US African American and Kenyan TNBC samples identifies differential expression in key oncogenic pathways. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4023. doi:10.1158/1538-7445.AM2013-4023