Genomic hallmarks of localized, non-indolent prostate cancer.

Fraser, Michael; Sabelnykova, Veronica Y; Yamaguchi, Takafumi N; Heisler, Lawrence E; Livingstone, Julie; Huang, Vincent; Shiah, Yu-Jia; Yousif, Fouad; Lin, Xihui; Masella, Andre P; Fox, Natalie S; Xie, Michael; Prokopec, Stephenie D; Berlin, Alejandro; Lalonde, Emilie; Ahmed, Musaddeque; Trudel, Dominique; Luo, Xuemei; Beck, Timothy A; Meng, Alice; ... (2017). Genomic hallmarks of localized, non-indolent prostate cancer. Nature, 541(7637), pp. 359-364. Macmillan Journals Ltd. 10.1038/nature20788

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Radiation Oncology

UniBE Contributor:

Dal Pra, Alan

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0028-0836

Publisher:

Macmillan Journals Ltd.

Language:

English

Submitter:

Beatrice Scheidegger

Date Deposited:

27 Feb 2018 11:46

Last Modified:

27 Feb 2018 11:46

Publisher DOI:

10.1038/nature20788

PubMed ID:

28068672

BORIS DOI:

10.7892/boris.109891

URI:

https://boris.unibe.ch/id/eprint/109891

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