Copy Number Profiles of Prostate Cancer in Men of Middle Eastern Ancestry

Simple Summary Prostate cancer is the most commonly diagnosed non-skin malignancy in men. Numerous studies have been undertaken to explore the role that genomics plays in prostate cancer initiation and progression. Most of this genomic data comes tumors arising in men with European or Asian ancestry, leaving other ancestry groups understudied. To fill this gap, we investigated the differences in copy number aberrations between prostate cancers arising in men of Middle Eastern ethnicity and those of European, African, or East Asian ethnicities in the hope of better understanding the incidence and risk of prostate cancer in different populations. We identified ancestry-specific gains and deletions, as well as differences in overall genomic instability between ancestry groups. This confirms that ancestry should be considered when investigating and characterizing biomarkers and molecular signatures relative to disease progression, prognosis, and potentially therapeutic targeting. Our knowledge of prostate cancer (PCa) genomics mainly reflects European (EUR) and Asian (ASN) populations. Our understanding of the influence of Middle Eastern (ME) and African (AFR) ancestry on the mutational profiles of prostate cancer is limited. To characterize genomic differences between ME, EUR, ASN, and AFR ancestry, fluorescent in situ hybridization (FISH) studies for NKX3-1 deletion and MYC amplification were carried out on 42 tumors arising in individuals of ME ancestry. These were supplemented by analysis of genome-wide copy number profiles of 401 tumors of all ancestries. FISH results of NKX3-1 and MYC were assessed in the ME cohort and compared to other ancestries. Gene level copy number aberrations (CNAs) for each sample were statistically compared between ancestry groups. NKX3-1 deletions by FISH were observed in 17/42 (17.5%) prostate tumors arising in men of ME ancestry, while MYC amplifications were only observed in 1/42 (2.3%). Using CNAs called from arrays, the incidence of NKX3-1 deletions was significantly lower in ME vs. other ancestries (20% vs. 52%; p = 2.3 x 10(-3)). Across the genome, tumors arising in men of ME ancestry had fewer CNAs than those in men of other ancestries (p = 0.014). Additionally, the somatic amplification of 21 specific genes was more frequent in tumors arising in men of ME vs. EUR ancestry (two-sided proportion test; Q < 0.05). Those included amplifications in the glutathione S-transferase family on chromosome 1 (GSTM1, GSTM2, GSTM5) and the IQ motif-containing family on chromosome 3 (IQCF1, IQCF2, IQCF13, IQCF4, IQCF5, IQCF6). Larger studies investigating ME populations are warranted to confirm these observations.