Genomic hallmarks of localized, non-indolent prostate cancer

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.

Alain Bergeron | Colin C. Collins | Mathieu Lupien | Natalie S. Fox | Paul C. Boutros | Emilie Lalonde | Francis Nguyen | Michael Fraser | Timothy A Beck | Daryl Waggott | Vincent Huang | Dominique Trudel | Clement Fung | Cenk Sahinalp | Syed Haider | Kathleen E. Houlahan | Andre P. Masella | Robert G. Bristow | Yu-Jia Shiah | Shadrielle Melijah G. Espiritu | Christine P’ng | Takafumi N. Yamaguchi | Housheng H. He | Christopher I. Cooper | John D. McPherson | Stephenie D. Prokopec | Kenneth C. Chu | Nicholas J. Harding | Richard de Borja | Christopher I Cooper | Haiying Kong | Michelle Sam | Shaylan K. Govind | Theodorus van der Kwast | Musaddeque Ahmed | Junyan Zhang | Louis Lacombe | Yves Fradet | Ken Kron | Veronica Y. Sabelnykova | Michèle Orain | Alejandro Berlin | J. McPherson | C. Collins | P. Boutros | R. Bristow | Daryl Waggott | M. Lupien | A. Berlin | L. Lacombe | A. Bergeron | C. Sahinalp | J. Hopkins | L. Heisler | Junyan Zhang | M. Chua | M. Fraser | Fouad Yousif | Syed Haider | H. He | Jeffrey E. Green | M. Sam | Nicholas Buchner | R. D. Borja | R. Denroche | N. Fleshner | N. Harding | Vincent Huang | Musaddeque Ahmed | Ken J. Kron | J. Livingstone | E. Lalonde | Constance H. Li | T. Kwast | Michelle A. Chan-Seng-Yue | A. Murison | Ren X. Sun | J. Johns | Xuemei Luo | A. Meng | Yu-Jia Shiah | D. Trudel | K. Chu | Haiying Kong | Y. Fradet | H. Hovington | Julie Livingstone | Neil E. Fleshner | Bernard Tetu | Taryne M. Chong | Ada Wong | F. Nguyen | Esther H. Jung | Clement Fung | A. D’Costa | Xihui Lin | A. D. Pra | Robert E. Denroche | Jeremy Johns | Lee Timms | Xihui Lin | M. Orain | V. Picard | Lawrence E. Heisler | Fouad Yousif | Valérie Picard | Alice Meng | Lawrence E Heisler | Michael Xie | Xuemei Luo | Timothy A. Beck | Alister D’Costa | Melvin L. K. Chua | Ada Wong | Taryne Chong | Nicholas B. Buchner | Helène Hovington | Alexander Murison | Bryan Lo | Julia F. Hopkins | Jeffrey Green | Esther Jung | Zhiyuan Wang | Alan Dal Pra | B. Lo | T. Kwast | Rob Bristow | S. Prokopec | B. Têtu | Michelle Sam | Lee E. Timms | Christine P'ng | Jeffrey Green | S. M. G. Espiritu | M. Ahmed | Michael Xie | Zhiyuan Wang | S. Haider | T. Yamaguchi | M. Chan-Seng-Yue | B. Lo | Francis Nguyen | Emilie Lalonde | Kenneth C. Chu | Cenk Sahinalp | Alejandro Berlin | Dominique Trudel | A. Masella | Junyan Zhang | A. Murison

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