Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-017-00377-y
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Funding
- Movember funds through Prostate Cancer Canada
- Ontario Institute for Cancer Research - Government of Ontario
- Ontario Institute for Cancer Research through Government of Ontario
- Princess Margaret Cancer Centre Foundation
- Radiation Medicine Program Academic Enrichment Fund
- Canadian Cancer Society Research Scientist Award
- Prostate Cancer Canada
- Movember Foundation [RS2014-01]
- Terry Fox Research Institute New Investigator Award
- CIHR New Investigator Award
- Genome Canada through a Large-Scale Applied Project
- German Federal Ministry of Education and Science [FKZ: 01KU1001A, FKZ: 01KU1001-B, FKZ: 01KU1001-C, FKZ: 01KU1001-D]
- Arvid Nilsson foundation
- Movember funds through Prostate Cancer Canada
- Ontario Institute for Cancer Research - Government of Ontario
- Ontario Institute for Cancer Research through Government of Ontario
- Princess Margaret Cancer Centre Foundation
- Radiation Medicine Program Academic Enrichment Fund
- Canadian Cancer Society Research Scientist Award
- Prostate Cancer Canada
- Movember Foundation [RS2014-01]
- Terry Fox Research Institute New Investigator Award
- CIHR New Investigator Award
- Genome Canada through a Large-Scale Applied Project
- German Federal Ministry of Education and Science [FKZ: 01KU1001A, FKZ: 01KU1001-B, FKZ: 01KU1001-C, FKZ: 01KU1001-D]
- Arvid Nilsson foundation
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Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer patients, and identify a median of one mitochondrial single-nucleotide variant (mtSNV) per patient. Some of these mtSNVs occur in recurrent mutational hotspots and associate with aggressive disease. Younger patients have fewer mtSNVs than those who diagnosed at an older age. We demonstrate strong links between mitochondrial and nuclear mutational profiles, with co-occurrence between specific mutations. For example, certain control region mtSNVs co-occur with gain of the MYC oncogene, and these mutations are jointly associated with patient survival. These data demonstrate frequent mitochondrial mutation in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer.
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