| Literature DB >> 28068672 |
Michael Fraser1, Veronica Y Sabelnykova2, Takafumi N Yamaguchi2, Lawrence E Heisler2, Julie Livingstone2, Vincent Huang2, Yu-Jia Shiah2, Fouad Yousif2, Xihui Lin2, Andre P Masella2, Natalie S Fox2,3, Michael Xie2, Stephenie D Prokopec2, Alejandro Berlin4, Emilie Lalonde2,3, Musaddeque Ahmed1, Dominique Trudel5, Xuemei Luo2, Timothy A Beck2, Alice Meng1, Junyan Zhang1, Alister D'Costa2, Robert E Denroche2, Haiying Kong2, Shadrielle Melijah G Espiritu2, Melvin L K Chua4, Ada Wong6, Taryne Chong6, Michelle Sam6, Jeremy Johns6, Lee Timms6, Nicholas B Buchner6, Michèle Orain7, Valérie Picard8, Helène Hovington8, Alexander Murison1, Ken Kron1, Nicholas J Harding2, Christine P'ng2, Kathleen E Houlahan2, Kenneth C Chu2, Bryan Lo2, Francis Nguyen2, Constance H Li2,3, Ren X Sun2,9, Richard de Borja2, Christopher I Cooper2, Julia F Hopkins2, Shaylan K Govind2, Clement Fung2, Daryl Waggott2, Jeffrey Green2, Syed Haider2, Michelle A Chan-Seng-Yue2, Esther Jung2, Zhiyuan Wang2, Alain Bergeron8, Alan Dal Pra4, Louis Lacombe8, Colin C Collins10,11, Cenk Sahinalp12, Mathieu Lupien1,3, Neil E Fleshner13, Housheng H He1,3, Yves Fradet8, Bernard Tetu7, Theodorus van der Kwast5, John D McPherson3,6, Robert G Bristow1,3,4, Paul C Boutros2,3,9.
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.Entities:
Mesh：
Year: 2017 PMID： 28068672 DOI： 10.1038/nature20788
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962