BACKGROUNDProstate 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.METHODSWe 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.RESULTSWe 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.CONCLUSIONSBesides 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. Prostate 76:349–358, 2016. © 2015 The Authors. The Prostate published by Wiley Periodicals, Inc.

Background The androgen‐regulated gene TMPRSS2 to the ETS transcription factor gene ERG fusion is the most common genomic alteration acquired during prostate tumorigenesis and biased toward men of European ancestry. In contrast, African American men present with more advanced disease, yet their tumors are less likely to acquire TMPRSS2‐ERG . Data for Africa is scarce. Methods RNA was made available for genomic analyses from 181 prostate tissue biopsy cores from Black South African men, 94 with and 87 without pathological evidence for prostate cancer. Reverse transcription polymerase chain reaction was used to screen for the TMPRSS2‐ERG fusion, while transcript junction coordinates and isoform frequencies, including novel gene fusions, were determined using targeted RNA sequencing. Results Here we report a frequency of 13% for TMPRSS2‐ERG in tumors from Black South Africans. Present in 12/94 positive versus 1/87 cancer negative prostate tissue cores, this suggests a 92.62% predictivity for a positive cancer diagnosis ( P = 0.0031). At a frequency of almost half that reported for African Americans and roughly a quarter of that reported for men of European ancestry, acquisition of TMPRSS2‐ERG appears to be inversely associated with aggressive prostate cancer. Further support was provided by linking the presence of TMPRSS2‐ERG to low‐grade disease in younger patients ( P = 0.0466), with higher expressing distal ERG fusion junction coordinates. Conclusions Only the second study of its kind for the African continent, we support a link between TMPRSS2‐ERG status and prostate cancer racial health disparity beyond the borders of the United States. We call for urgent evaluation of androgen deprivation therapy within Africa.

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20–40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research.