Mitochondrial mutations drive prostate cancer aggression
Standard
Mitochondrial mutations drive prostate cancer aggression. / Hopkins, Julia F; Sabelnykova, Veronica Y; Weischenfeldt, Joachim; Simon, Ronald; Aguiar, Jennifer A; Alkallas, Rached; Heisler, Lawrence E; Zhang, Junyan; Watson, John D; Chua, Melvin L K; Fraser, Michael; Favero, Francesco; Lawerenz, Chris; Plass, Christoph; Sauter, Guido; McPherson, John D; van der Kwast, Theodorus; Korbel, Jan; Schlomm, Thorsten; Bristow, Robert G; Boutros, Paul C.
in: NAT COMMUN, Jahrgang 8, Nr. 1, 22.09.2017, S. 656.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Mitochondrial mutations drive prostate cancer aggression
AU - Hopkins, Julia F
AU - Sabelnykova, Veronica Y
AU - Weischenfeldt, Joachim
AU - Simon, Ronald
AU - Aguiar, Jennifer A
AU - Alkallas, Rached
AU - Heisler, Lawrence E
AU - Zhang, Junyan
AU - Watson, John D
AU - Chua, Melvin L K
AU - Fraser, Michael
AU - Favero, Francesco
AU - Lawerenz, Chris
AU - Plass, Christoph
AU - Sauter, Guido
AU - McPherson, John D
AU - van der Kwast, Theodorus
AU - Korbel, Jan
AU - Schlomm, Thorsten
AU - Bristow, Robert G
AU - Boutros, Paul C
PY - 2017/9/22
Y1 - 2017/9/22
N2 - 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.In prostate cancer, the role of mutations in the maternally-inherited mitochondrial genome are not well known. Here, the authors demonstrate frequent, age-dependent mitochondrial mutation in prostate cancer. Strong links between mitochondrial and nuclear mutational profiles are associated with clinical aggressivity.
AB - 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.In prostate cancer, the role of mutations in the maternally-inherited mitochondrial genome are not well known. Here, the authors demonstrate frequent, age-dependent mitochondrial mutation in prostate cancer. Strong links between mitochondrial and nuclear mutational profiles are associated with clinical aggressivity.
KW - Journal Article
U2 - 10.1038/s41467-017-00377-y
DO - 10.1038/s41467-017-00377-y
M3 - SCORING: Journal article
C2 - 28939825
VL - 8
SP - 656
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -