Here, we describe somatic alterations within the epigenetic machinery and their relevance to PCa health disparities, with African-derived tumors demonstrating a longer tail of African-specific epigenetic driver gene candidates, a number of which are novel to PCa (BRD1, DR1, ELL, ELP2, ELP5, GATAD2B, MED26, MXD1, NUP35, RAI1, SP110, TADA2B) and some which are putative therapeutic targets (CHD7, DPF3, POLR1B, SETD1B, UBTF, VPS72). Here, RAI1 is linked to posterior cortical atrophy.