Abstract Prostate cancer is the most common non-cutaneous cancer among men. A man with 1,2 or 3 first degree relatives with prostate cancer, has a 2,5, and 11-fold increased risk of developing prostate cancer. The heritability rate of prostate cancer is 58%. African American men have the highest incidence and mortality rate of prostate cancer in American. Men of African descent, globally, are more likely to die from prostate cancer than any other ancestral groups. We performed Immunohistochemistry(IHC) and RNA seq analysis on African American tissue and serum samples, with a focus on HMGA2, which has been shown promote EMT, invasion, and metastasis in cancer. Acknowledgements: These studies were supported by NIH/NIMHD U54MD007590 and U54MD013376. Our sample set included 3 benign and 2 prostate cancer tumors from African Americans. IHC markers showed HMGA2 staining within epithelial cells of the prostate cancer tissue. This result validates studies that show that distinct subtypes of prostate cancer may arise from luminal and basal epithelial cell types. RNA seq results showed HMGA to be non-significantly down-regulated in tumor samples. The most differentially expressed (DE) gene, however, was SNORD116-18. Studies have shown SNORD116-18 expression to be associated with chronic lymphocytic leukemia in distinguishing prognostic groups. This finding may be a pathway of interest for further studies. RNA seq of serum gave homogeneous results, however, gene set enrichment analysis of the most differentially expressed genes within the serum showed overlap with inflammation pathways gene for upregulated DE genes and Methylation Pathway for downregulated DE genes. Further analysis on more samples from African Americans tissue and serum will be used to validate findings. Citation Format: Maxine S. Harlemon, Roni Bollag, Martha Terris, Ana Cecilia Millena, Nathan Bowen, Valerie Odero-Marah. A case and control genetic profile of tissue and serum in African American men [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C044.