Abstract D120: Similarities and differences between genomic profiles of prostate cancers from African American and European American men with implications for precision cancer medicine

Abstract

Abstract Background: African American (AA) men have the highest mortality rate from prostate cancer compared to men from other races. Differences in the spectrum of somatic genomic alterations in tumors between AA men differs from non-AA men has not been well characterized as relatively few AA men have been included in prostate cancer genomic studies. To address this, we examined 5 publicly-available and commercial genomic datasets containing AA men with prostate cancer to identify novel alterations associated with race. Methods: In a meta-analysis of 4 public datasets, we investigated the mutational frequencies of 14 genes across 252 AA men and 635 non-AA men with primary prostate cancer. We also examined genomic alterations from the tumors of 436 AA men and 3018 EA men with primary or metastatic prostate cancer using the Foundation One assay. Results: We identified mutations in ZFHX3 and focal deletions in ETV3 more frequently in tumors from AA patients. The mutational frequency of TP53 was strongly associated with increasing Gleason grade. Using the commercial assay, we identified alterations in PTEN and TMPRSS2-ERG as less frequent in AA patients compared to non-AA patients in both primary and metastatic tumors. MYC amplifications were more frequent in AA patients with metastatic prostate cancer. Furthermore, we found that genomic alterations in KMT2D and CCND1 were more frequent in primary prostate tumors from AA patients, resulting in differential cell cycle genes and KMT alterations. MYC amplifications were more frequent in AA patients with metastatic prostate cancer. Genomic alterations in DNA repair genes were found at similar frequencies between EA and AA patients. Conclusion: While these results indicate that differences in mutational profiles may exist between racial groups in prostate cancers, additional sequencing studies that profile AA and EA men from the same clinical setting and that are matched for clinical covariates may be needed to confirm these findings. Overall, these results have implications for applying precision cancer medicine in AA prostate cancer patients. Citation Format: Yusuke Koga, Hanbing Song, Zachary Chalmers, Justin Newberg, Garrett Frampton, Joshua Campbell, Franklin Huang. Similarities and differences between genomic profiles of prostate cancers from African American and European American men with implications for precision cancer medicine [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D120.