Racial differences in genomic profiling of prostate cancer at the durham veterans affairs medical center.

Abstract

e17002 Background: Black men are underrepresented in precision oncology studies. Mahal et al. found that black men with metastatic PCa who had genomic profiling (GP) more commonly had mutations in DNA damage repair (DDR) and actionable genes, although only 8.5% of men in the study were black. [i] Here, we examine racial differences in GP in men with PCa at the Durham Veterans Affairs Medical Center (DVAMC). Methods: Men with PCa who had GP completed by Foundation Medicine at DVAMC from 2/2019-2/2022 were included. Reports were analyzed for mutations of interest. Biopsy site and patient demographics were extracted on chart review. Results: 155 men had GP at the DVAMC during the study period. Importantly 88 (57%) men were black and 67 (43%) were white. Sequencing was performed on the primary tumor (n = 80, 52%), metastatic site (n = 25, 16%), or circulating tumor (ct) DNA (n = 50, 32%). GP was performed on both tissue and ctDNA in 8% of patients, 58% had concordant findings. Racial differences in actionable mutations, DDR mutations, and mutations approved for PARP inhibitor use are noted in Table. The most commonly altered gene is TP53 (n = 59), more prevalent in black men (n = 36, 61%). ATM mutations are more common in black men, 10/14 (71%), however 85% of these are identified on ctDNA and n = 5 had an allele fraction of < 1% suggestive of clonal hematopoiesis of indeterminate potential (CHIP). In contrast, 8/9 (89%) of PIK3CA mutations and 25/36 (69%) of TMPRSS fusions were found in white men. Conclusions: Black men comprised a majority of the patients with PCa who had GP at the DVAMC. We found no statistically significant differences between black and white men in incidence of actionable mutations, DDR mutations, or mutations approved for PARP inhibitor use. PIK3CA alterations and TMPRSS fusions are enriched in white men, consistent with published literature, however, ATM and TP53 mutations are enriched in black men, discordant with findings from Mahal et al,raising the possibility that GP in veterans differs due to environmental exposures. ATM mutations are predominantly found in ctDNA, which may represent CHIP. Expansion of the above analysis could offer insight into racial differences in tumor biology.[Table: see text]