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Nature. 2017 Jan 19;541(7637):359-364. doi: 10.1038/nature20788. Epub 2017 Jan 9.

Genomic hallmarks of localized, non-indolent prostate cancer.

Author information

1
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
2
Informatics &Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Canada.
3
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
4
Department of Radiation Oncology, University of Toronto, Toronto, Canada.
5
Department of Pathology and Laboratory Medicine, Toronto General Hospital/University Health Network, Toronto, Canada.
6
Genome Technologies Program, Ontario Institute for Cancer Research, Toronto, Canada.
7
Department of Pathology and Research Centre of CHU de Québec-Université Laval. Québec City, Canada.
8
Division of Urology and Research Centre of CHU de Québec-Université Laval, Québec City, Canada.
9
Department of Pharmacology &Toxicology, University of Toronto, Toronto, Canada.
10
Department of Urologic Sciences, University of British Columbia, Vancouver, Canada.
11
Vancouver Prostate Centre, Vancouver, Canada.
12
School of Computing Science, Simon Fraser University, Burnaby, Canada.
13
Division of Urology, Princess Margaret Cancer Centre/University Health Network, Toronto, Canada.

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.

PMID:
28068672
DOI:
10.1038/nature20788
[Indexed for MEDLINE]

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