title: Spectrum of mitochondrial genomic variation and associated clinical presentation of prostate cancer in South African men.
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.
authors.affiliation: J. Craig Venter Institute, La Jolla, California.
authors.forename: John P
authors.initials: JP
authors.lastname: McCrow
authors.affiliation: J. Craig Venter Institute, La Jolla, California.|Laboratory for Human Comparative and Prostate Cancer Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia.|Faculty of Medicine, University of New South, Wales Australia, Randwick, NSW, Australia.
authors.forename: Desiree C
authors.initials: DC
authors.lastname: Petersen
authors.affiliation: Department of Pathology, University of Pretoria, South Africa.
authors.forename: Melanie
authors.initials: M
authors.lastname: Louw
authors.affiliation: Laboratory for Human Comparative and Prostate Cancer Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia.|Faculty of Medicine, University of New South, Wales Australia, Randwick, NSW, Australia.
authors.forename: Eva K F
authors.initials: EK
authors.lastname: Chan
authors.affiliation: J. Craig Venter Institute, La Jolla, California.|Laboratory for Human Comparative and Prostate Cancer Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Harmeyer
authors.affiliation: Laboratory for Human Comparative and Prostate Cancer Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vecchiarelli
authors.affiliation: Laboratory for Human Comparative and Prostate Cancer Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia.
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Lyons
authors.affiliation: School of Health Systems and Public Health, University of Pretoria, South Africa.
authors.forename: M S Riana
authors.initials: MS
authors.lastname: Bornman
authors.affiliation: J. Craig Venter Institute, La Jolla, California.|Laboratory for Human Comparative and Prostate Cancer Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia.|Faculty of Medicine, University of New South, Wales Australia, Randwick, NSW, Australia.|School of Health Systems and Public Health, University of Pretoria, South Africa.|Central Clinical School, University of Sydney, Camperdown, Sydney, NSW, Australia.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hayes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044383:Black People; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D054629:Genome, Mitochondrial / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D013019:South Africa; D044465:White People; D001741:Black or African American
chemical_list: D004272:DNA, Mitochondrial; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: African ancestry; mitochondria; outcomes; prostate cancer; variation