Genomic hallmarks of localized, non-indolent prostate cancer

Michael Fraser, Veronica Y. Sabelnykova, Takafumi N. Yamaguchi, Lawrence E. Heisler, Julie Livingstone, Vincent Huang, Yu-Jia Shiah, Fouad Yousif, Xihui Lin, Andre P. Masella, Natalie S. Fox, Michael Xie, Stephenie D. Prokopec, Alejandro Berlin, Emilie Lalonde, Musaddeque Ahmed, Dominique Trudel, Xuemei Luo, Timothy A. Beck, Alice Meng, Junyan Zhang, Alister D’Costa, Robert E. Denroche, Haiying Kong, Shadrielle Melijah G. Espiritu, Melvin L. K. Chua, Ada Wong, Taryne Chong, Michelle Sam, Jeremy Johns, Lee Timms, Nicholas B. Buchner, Michèle Orain, Valérie Picard, Helène Hovington, Alexander Murison, Ken Kron, Nicholas J. Harding, Christine P’ng, Kathleen E. Houlahan, Kenneth C. Chu, Bryan Lo, Francis Nguyen, Constance H. Li, Ren X. Sun, Richard de Borja, Christopher I. Cooper, Julia F. Hopkins, Shaylan K. Govind, Clement Fung, Daryl Waggott, Jeffrey Green, Syed Haider, Michelle A. Chan-Seng-Yue, Esther Jung, Zhiyuan Wang, Alain Bergeron, Alan Dal Pra, Louis Lacombe, Colin C. Collins, Cenk Sahinalp, Mathieu Lupien, Neil E. Fleshner, Housheng H. He, Yves Fradet, Bernard Tetu, Theodorus van der Kwast, John D. McPherson, Robert G. Bristow () and Paul C. Boutros ()
Additional contact information
Michael Fraser: Princess Margaret Cancer Centre, University Health Network
Veronica Y. Sabelnykova: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Takafumi N. Yamaguchi: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Lawrence E. Heisler: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Julie Livingstone: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Vincent Huang: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Yu-Jia Shiah: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Fouad Yousif: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Xihui Lin: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Andre P. Masella: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Natalie S. Fox: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Michael Xie: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Stephenie D. Prokopec: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Alejandro Berlin: University of Toronto
Emilie Lalonde: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Musaddeque Ahmed: Princess Margaret Cancer Centre, University Health Network
Dominique Trudel: Toronto General Hospital/University Health Network
Xuemei Luo: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Timothy A. Beck: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Alice Meng: Princess Margaret Cancer Centre, University Health Network
Junyan Zhang: Princess Margaret Cancer Centre, University Health Network
Alister D’Costa: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Robert E. Denroche: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Haiying Kong: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Shadrielle Melijah G. Espiritu: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Melvin L. K. Chua: University of Toronto
Ada Wong: Genome Technologies Program, Ontario Institute for Cancer Research
Taryne Chong: Genome Technologies Program, Ontario Institute for Cancer Research
Michelle Sam: Genome Technologies Program, Ontario Institute for Cancer Research
Jeremy Johns: Genome Technologies Program, Ontario Institute for Cancer Research
Lee Timms: Genome Technologies Program, Ontario Institute for Cancer Research
Nicholas B. Buchner: Genome Technologies Program, Ontario Institute for Cancer Research
Michèle Orain: Department of Pathology and Research Centre of CHU de Québec-Université Laval
Valérie Picard: Division of Urology and Research Centre of CHU de Québec-Université Laval
Helène Hovington: Division of Urology and Research Centre of CHU de Québec-Université Laval
Alexander Murison: Princess Margaret Cancer Centre, University Health Network
Ken Kron: Princess Margaret Cancer Centre, University Health Network
Nicholas J. Harding: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Christine P’ng: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Kathleen E. Houlahan: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Kenneth C. Chu: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Bryan Lo: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Francis Nguyen: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Constance H. Li: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Ren X. Sun: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Richard de Borja: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Christopher I. Cooper: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Julia F. Hopkins: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Shaylan K. Govind: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Clement Fung: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Daryl Waggott: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Jeffrey Green: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Syed Haider: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Michelle A. Chan-Seng-Yue: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Esther Jung: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Zhiyuan Wang: Informatics & Biocomputing Program, Ontario Institute for Cancer Research
Alain Bergeron: Division of Urology and Research Centre of CHU de Québec-Université Laval
Alan Dal Pra: University of Toronto
Louis Lacombe: Division of Urology and Research Centre of CHU de Québec-Université Laval
Colin C. Collins: University of British Columbia
Cenk Sahinalp: School of Computing Science, Simon Fraser University
Mathieu Lupien: Princess Margaret Cancer Centre, University Health Network
Neil E. Fleshner: Princess Margaret Cancer Centre/University Health Network
Housheng H. He: Princess Margaret Cancer Centre, University Health Network
Yves Fradet: Division of Urology and Research Centre of CHU de Québec-Université Laval
Bernard Tetu: Department of Pathology and Research Centre of CHU de Québec-Université Laval
Theodorus van der Kwast: Toronto General Hospital/University Health Network
John D. McPherson: University of Toronto
Robert G. Bristow: Princess Margaret Cancer Centre, University Health Network
Paul C. Boutros: Informatics & Biocomputing Program, Ontario Institute for Cancer Research

Nature, 2017, vol. 541, issue 7637, 359-364

Abstract: Abstract Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.

Date: 2017
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DOI: 10.1038/nature20788

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