Genetic fingerprint could identify which men with prostate cancer may develop aggressive disease

Researchers have discovered the genetic fingerprint that may account for why up to 30% of men with potentially curable, localized prostate cancer go on to develop aggressive disease that spreads after radiotherapy or surgery. Their results are published online in Nature, and may help clinicians successfully personalize treatment with effective and targeted therapies from the moment patients are diagnosed.

Researchers at Laval University, Quebec City, Canada, analyzed tumors from 500 men from the general population who were diagnosed with localized, non-inherited prostate cancer. In a related study published in Nature Communications, researchers also “cracked” the genetic code showing why BRCA2 inherited disease can become lethal in rare cases, in which men have inherited a BRCA2 gene mutation that affects DNA cellular damage repair.

“We used specialized state-of-the-art DNA sequencing techniques to focus on the genetics of prostate cancers to better understand what is so different from one man’s disease to another man’s disease,” said co-principal investigator Robert Bristow, MD, PhD, FRCPC, clinician-scientist, Princess Margaret Cancer Centre, University Health Network; and professor, Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Ontario, Canada.

“These genetic fingerprints had high accuracy in being able to discern those men who do well with surgery or radiotherapy and those men that already have early spread of their disease outside the prostate gland. This information gives us new precision about the treatment response of men with prostate cancer, and important clues as to how to better treat one set of men versus the other to improve cure rates overall.”

Dr. Bristow co-leads the Canadian Prostate Cancer Genome Network (CPC-GENE), the world-leading prostate cancer sequencing program, along with co-principal investigator Paul Boutros, PhD, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

He and fellow researchers have also previously identified the first molecular portrait of localized, multi-focal prostate cancer and a new gene subgroup driving it (Nature Genetics, May 25, 2015); and the development of a genetic test to identify which men are at highest risk for their prostate cancer to recur after localized treatment with surgery or radiotherapy (Lancet Oncology, Nov 13, 2014).

Dr. Bristow noted that worldwide, over 200,000 men die from prostate cancer each year, despite the fact that most present with localized, potentially curable disease.

“The richness of information in our genetic findings today will enable us to further sort individual patients into appropriate groups of risk for spread of their disease and effect cures in men who otherwise might have been incurable,” he concluded.

This research was supported by Movember funds through Prostate Cancer Canada, the Ontario Institute for Cancer Research, the Canadian Institutes for Health Research, the Canadian Cancer Society, and The Princess Margaret Cancer Foundation.