Mitochondrial mutations drive prostate cancer aggression

Julia F. Hopkins, Veronica Y. Sabelnykova, Joachim Weischenfeldt, Ronald Simon, Jennifer A. Aguiar, Rached Alkallas, Lawrence E. Heisler, Junyan Zhang, John D. Watson, Melvin L.K. Chua, Michael Fraser, Francesco Favero, Chris Lawerenz, Christoph Plass, Guido Sauter, John Douglas Mcpherson, Theodorus Van Der Kwast, Jan Korbel, Thorsten Schlomm, Robert G. BristowPaul C. Boutros

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number656
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Hopkins, J. F., Sabelnykova, V. Y., Weischenfeldt, J., Simon, R., Aguiar, J. A., Alkallas, R., Heisler, L. E., Zhang, J., Watson, J. D., Chua, M. L. K., Fraser, M., Favero, F., Lawerenz, C., Plass, C., Sauter, G., Mcpherson, J. D., Van Der Kwast, T., Korbel, J., Schlomm, T., ... Boutros, P. C. (2017). Mitochondrial mutations drive prostate cancer aggression. Nature Communications, 8(1), [656]. https://doi.org/10.1038/s41467-017-00377-y