Abstract:
BACKGROUND : Prostate cancer incidence and mortality rates are significantly increased in
African–American men, but limited studies have been performed within Sub–Saharan
African populations. As mitochondria control energy metabolism and apoptosis we speculate
that somatic mutations within mitochondrial genomes are candidate drivers of aggressive
prostate carcinogenesis.
METHODS : We used matched blood and prostate tissue samples from 87 South African men
(77 with African ancestry) to perform deep sequencing of complete mitochondrial genomes.
Clinical presentation was biased toward aggressive disease (Gleason score >7, 64%), and
compared with men without prostate cancer either with or without benign prostatic hyperplasia.
RESULTS : We identified 144 somatic mtDNA single nucleotide variants (SNVs), of which 80
were observed in 39 men presenting with aggressive disease. Both the number and frequency
of somatic mtDNA SNVs were associated with higher pathological stage.
CONCLUSIONS : Besides doubling the total number of somatic PCa-associated mitochondrial
genome mutations identified to date, we associate mutational load with aggressive
prostate cancer status in men of African ancestry.
