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 D. McPherson; Theodorus Van Der Kwast; Jan Korbel; Thorsten Schlomm; Robert G. Bristow; Paul C. Boutros

doi:10.1038/s41467-017-00377-y

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 D. McPherson, Theodorus Van Der Kwast, Jan Korbel, Thorsten Schlomm, Robert G. BristowPaul C. Boutros

^*Corresponding author for this work

38 Citations (Scopus)

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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 language	English
Article number	656
Journal	Nature Communications
Volume	8
Issue number	1
Number of pages	8
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-017-00377-y
Publication status	Published - 1 Dec 2017

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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

Hopkins, JF, Sabelnykova, VY, Weischenfeldt, J, Simon, R, Aguiar, JA, Alkallas, R, Heisler, LE, Zhang, J, Watson, JD, Chua, MLK, Fraser, M, Favero, F, Lawerenz, C, Plass, C, Sauter, G, McPherson, JD, Van Der Kwast, T, Korbel, J, Schlomm, T, Bristow, RG & Boutros, PC 2017, 'Mitochondrial mutations drive prostate cancer aggression', Nature Communications, vol. 8, no. 1, 656. https://doi.org/10.1038/s41467-017-00377-y

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title = "Mitochondrial mutations drive prostate cancer aggression",

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.",

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

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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.

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Y1 - 2017/12/1

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.

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.

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DO - 10.1038/s41467-017-00377-y

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SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 656

ER -

Mitochondrial mutations drive prostate cancer aggression

Abstract

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