Genomic Profiling of Prostate Cancers from Men with African and European Ancestry.

Abstract

African American (AFR) men have the highest mortality rate from prostate cancer (PCa) compared with men of other racial/ancestral groups. Differences in the spectrum of somatic genome alterations in tumors between AFR men and other populations have not been well-characterized due to a lack of inclusion of significant numbers in genomic studies. To identify genomic alterations associated with race, we compared the frequencies of somatic alterations in PCa obtained from four publicly available datasets comprising 250 AFR and 611 European American (EUR) men and a targeted sequencing dataset from a commercial platform of 436 AFR and 3018 EUR men. Mutations in <i>ZFHX3</i> as well as focal deletions in <i>ETV3</i> were more frequent in tumors from AFR men. <i>TP53</i> mutations were associated with increasing Gleason score. <i>MYC</i> amplifications were more frequent in tumors from AFR men with metastatic PCa, whereas deletions in <i>PTEN</i> and rearrangements in <i>TMPRSS2-ERG</i> were less frequent in tumors from AFR men. <i>KMT2D</i> truncations and <i>CCND1</i> amplifications were more frequent in primary PCa from AFR men. Genomic features that could impact clinical decision making were not significantly different between the two groups including tumor mutation burden, MSI status, and genomic alterations in select DNA repair genes, <i>CDK12</i>, and in <i>AR</i>. Although we identified some novel differences in AFR men compared with other populations, the frequencies of genomic alterations in current therapeutic targets for PCa were similar between AFR and EUR men, suggesting that existing precision medicine approaches could be equally beneficial if applied equitably.