skip to main content
Research Highlight | May 24, 2017

Canadian study identifies predictive genomic signature for high-risk prostate cancer

Prostate cancer

Understanding why some prostate cancer tumours are indolent while others eventually kill patients is the focus of many within the global cancer research community. A top Canadian research team has provided new answers with the potential to change the way aggressive tumours are treated and, importantly, improve cure rates.

The study was conducted by a TFRI and Prostate Cancer Canada funded research team led by Drs. Robert Bristow (Princess Margaret Cancer Centre) and Paul Boutros (Ontario Institute for Cancer Research), and was published in Nature in January 2017. 

The team revealed for first time that the complexity of the prostate genome can be used to predict whether patients with localized and non-indolent prostate cancers will have more or less aggressive cancers. Improving this understanding could allow researchers to figure out how to deploy existing therapies more precisely; for example, triaging treatment based on defined prostate cancer subtypes. Further, it may provide novel candidate targets for creating new intensified therapies to increase cures in those patients at greatest risk of death.

Prostate cancer remains the most frequently diagnosed non-skin cancer in Canadian men, and its incidence continues to grow as the population ages. Around 30 per cent of men relapse despite successful initial treatment, and current clinical prognostics cannot explain why. To counter this, the team took a novel approach to the analysis in the present study: rather than focusing on small subsets of the genome, information present in all of the DNA was used to come up with a predictive signature that accurately describes the complexity of prostate cancers. The signature comprises numerous molecular aberrations that outperformed well-described prognostic biomarkers for the disease.

Two hundred whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles were examined.  Numerous molecular aberrations that indicated disease recurrence were identified and could be used in determining disease prognosis. Further, local hypermutation events that correlated with specific genomic profiles often occurred.

The research team defined 40 properties of prostate cancers, including mutation density, presence/absence of chromothripsis and kataegis and a series of recurrent somatic mutations. The team’s data also highlights the differences in mutational profiles between localized intermediate risk cancers and metastatic castrate resistant prostate cancer.

The present study furthers the ability to understand why some prostate cancers are aggressive, and despite the best available treatments may go on to kill the patient, while others are adequately treated by precision radiotherapy or surgery alone. Besides furthering the field of precision medicine and potentially changing the way aggressive prostate cancers are treated, this data will also serve as a major genomic resource for groups around the world.

Study: Genomic hallmarks of localized, non-indolent prostate cancer

Authors: 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. Espirit, 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 Gree, 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. He1, Yves Fradet, Bernard Tetu, Theodorus van der Kwast, John D. McPherson, Robert G. Bristow & Paul C. Boutros.

Funding: P.C.B. was supported by a Terry Fox Research Institute New Investigator Award and a CIHR New Investigator Award. D.T. was part of the Terry Fox Foundation Strategic Health Research Training Program in Cancer Research at the Canadian Institute of Health Research and Ontario Institute for Cancer Research.

TFRI Links, Spring 2017