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Mitochondrial mutations drive prostate cancer aggression

Publikation: Forskning - peer reviewTidsskriftartikel

Dokumenter

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 D. McPherson, Theodorus Van Der Kwast, Jan Korbel, Thorsten Schlomm, Robert G. Bristow & 1 andre Paul C. Boutros

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.
OriginalsprogEngelsk
Artikelnummer656
TidsskriftNature Communications
Vol/bind8
Tidsskriftsnummer1
Antal sider8
ISSN2041-1723
DOI
StatusUdgivet - 1 dec. 2017

ID: 185036843