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dc.contributor.authorKalsbeek, AMF
dc.contributor.authorChan, EKF
dc.contributor.authorCorcoran, NM
dc.contributor.authorHovens, CM
dc.contributor.authorHayes, VM
dc.date.accessioned2020-12-21T03:14:49Z
dc.date.available2020-12-21T03:14:49Z
dc.date.issued2017-09-19
dc.identifierpii: 19926
dc.identifier.citationKalsbeek, A. M. F., Chan, E. K. F., Corcoran, N. M., Hovens, C. M. & Hayes, V. M. (2017). Mitochondrial genome variation and prostate cancer: a review of the mutational landscape and application to clinical management. ONCOTARGET, 8 (41), pp.71342-71357. https://doi.org/10.18632/oncotarget.19926.
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/11343/257127
dc.description.abstractProstate cancer is a genetic disease. While next generation sequencing has allowed for the emergence of molecular taxonomy, classification is restricted to the nuclear genome. Mutations within the maternally inherited mitochondrial genome are known to impact cancer pathogenesis, as a result of disturbances in energy metabolism and apoptosis. With a higher mutation rate, limited repair and increased copy number compared to the nuclear genome, the clinical relevance of mitochondrial DNA (mtDNA) variation requires deeper exploration. Here we provide a systematic review of the landscape of prostate cancer associated mtDNA variation. While the jury is still out on the association between inherited mtDNA variation and prostate cancer risk, we collate a total of 749 uniquely reported prostate cancer associated somatic mutations. Support exists for number of somatic events, extent of heteroplasmy, and rate of recurrence of mtDNA mutations, increasing with disease aggression. While, the predicted pathogenic impact for recurrent prostate cancer associated mutations appears negligible, evidence exists for carcinogenic mutations impacting the cytochrome c oxidase complex and regulating metastasis through elevated reactive oxygen species production. Due to a lack of lethal cohort analyses, we provide additional unpublished data for metastatic disease. Discussing the advantages of mtDNA as a prostate cancer biomarker, we provide a review of current progress of including elevated mtDNA levels, of a large somatic deletion, acquired tRNAs mutations, heteroplasmy and total number of somatic events (mutational load). We confirm via meta-analysis a significant association between mtDNA mutational load and pathological staging at diagnosis or surgery (p < 0.0001).
dc.languageEnglish
dc.publisherIMPACT JOURNALS LLC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleMitochondrial genome variation and prostate cancer: a review of the mutational landscape and application to clinical management
dc.typeJournal Article
dc.identifier.doi10.18632/oncotarget.19926
melbourne.affiliation.departmentSurgery (RMH)
melbourne.source.titleOncotarget
melbourne.source.volume8
melbourne.source.issue41
melbourne.source.pages71342-71357
dc.rights.licenseCC BY
melbourne.elementsid1245940
melbourne.contributor.authorHovens, Christopher
melbourne.contributor.authorCorcoran, Niall
dc.identifier.eissn1949-2553
melbourne.accessrightsOpen Access


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