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

Abstract

Purpose: 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. Experimental Design: 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. Results: Mutations in ZFHX3 as well as focal deletions in ETV3 were more frequent in tumors from AFR men. TP53 mutations were associated with increasing Gleason score. MYC amplifications were more frequent in tumors from AFR men with metastatic PCa, whereas deletions in PTEN and rearrangements in TMPRSS2-ERG were less frequent in tumors from AFR men. KMT2D truncations and CCND1 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, CDK12, and in AR. Conclusions: 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.

Cancer Omics in Africa: Present and Prospects

“…In contrast, tumor mutation burden, microsatellite instability (MSI) status, and genomic alterations in select DNA repair genes, Cyclin Dependent Kinase 12 (CDK12), and in Androgen receptor (AR), which are the genomic features that could influence the clinical decisions, were found not to differ significantly between the two groups studied. Despite the results indicating genomic disparities amongst AA and EA, the similarities found in the frequencies of genomic alterations in PCa therapeutic targets, suggest that precision medicine strategies could be evenly useful if applied fairly (25).…”

A Competing Risk Nomogram for Predicting Cancer-Specific Survival Among Patients with Prostate Cancer after Radical Prostatectomy

“…For example, In the United States, PCa tended to be larger in African Americans and was more likely to metastasize than white men [38]. From a genetic perspective, some gene mutations related to disease progression are more common in African Americans, such as TP53 mutations and MYC ampli cation [39]. Several risk-associated single nucleotide polymorphisms were found to be overexpressed in African Americans [40].…”

Early-onset metastatic and clinically advanced prostate cancer is a distinct clinical and molecular entity characterized by increased TMPRSS2–ERG fusions

“…Comprehensive genomic profiling was performed by Foundation Medicine, Inc. as previously described [11]. Tumor mutational burden (TMB), microsatellite instability (MSI), and patient ancestry were determined as previously described [12][13][14]. TMB cutoffs were defined as: low TMB (<6.0 Mutations/Mb), intermediate TMB (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) Mutations/ Mb), and high TMB (≥20 Mutations/Mb).…”