Author: ["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","Paul C. Boutros"]
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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. Genomic analyses of localized, non-indolent prostate cancer identify recurrent aberrations that can predict relapse, and also highlight differences between early prostate cancer and metastatic, castration-resistant disease. Robert Bristow, Paul Boutros and colleagues report genomic analyses of localized, non-indolent prostate cancer, which is a common disease state at initial clinical presentation that shows intermediate risk and cure rates. The analyses include 200 whole-genome and 477 whole-exome sequences of localized prostate cancer tumours, and analyses of copy-number alterations, genomic rearrangements and methylation. The authors highlight differences in mutational profiles between localized intermediate risk and metastatic, castrate-resistant prostate cancer.Cite this article
Fraser, M., Sabelnykova, V., Yamaguchi, T. et al. Genomic hallmarks of localized, non-indolent prostate cancer. Nature 541, 359–364 (2017). https://doi.org/10.1038/nature20788 