Abstract Recent investigations on patient race have begun to characterize biological differences in prostate cancer, particularly among patients of African ancestry. Despite clinical trends continuously demonstrating this health disparity, very few African American cell line models exist for downstream molecular investigations, and even fewer have undergone proper characterization of their expression profiles. Here, we characterize the transcriptome of the non-malignant RC-77 N/E and malignant RC-77 T/E prostate epithelial cell lines previously established from prostate specimens from the same African American patient with early-stage primary prostate cancer. Total RNA sequencing was performed on the paired cell lines using Illumina NextSeq 2000 P2 to build transcriptomic profiles that have previously been undetermined. Following data analysis and normalization, we identified 369 genes with significant upregulation in the RC-77 T/E cell line in comparison to its normal counterpart. Among the top 15 upregulated genes, half of them were previously characterized in prostate cancer but not in the context of patient race. We further compared the transcriptome of RC-77 T/E to that of the African American metastatic MDA-PCa-2b. Finally, we analyzed differential gene expression by race among prostate cancer patients in The Cancer Genome Atlas (TCGA) to correlate our transcriptomics findings on the cell line level with that on the population level. These findings may allow for more targeted assessments of genes that are dependent on race as molecular tools are established to narrow the health disparities gap in prostate cancer. Citation Format: Kristi Y. Lee, Erica L. Beatson, Cindy H. Chau, Douglas K. Price, William D. Figg. Whole transcriptome analysis of paired African American prostate cancer cell lines [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A045.