A team of researchers and clinician-scientists from across Canada have discovered a signature of 41 mutations that are common in prostate cancer and will help to prevent patients with non-aggressive disease from being overtreated. Dr. Paul Boutros, a Principal Investigator in OICR’s Informatics and Bio-computing Program and Co-Lead of the Canadian Prostate Cancer Genome Network (CPC-GENE), answered a few questions about how the signature was developed and its potential impact on patients.
Can you provide a brief overview of the research that was recently published?
One in every eight Canadian men will be diagnosed with prostate cancer during their lifetime. However many of these tumours are slow growing and as a result many patients are overtreated. Overtreating these less-aggressive tumours can result in long-term side effects and a decreased quality of life for patients. Treating these side effects and providing unnecessary treatment in the first place also puts a burden on the healthcare system.
To understand what makes some prostate cancers aggressive, we used new DNA sequencing technologies to search for mutations in a group of 200 Canadian prostate cancer patients. We created sophisticated computational algorithms to check if each of the three billion bases of the human genome were mutated. From the complete dataset of about 60 trillion data-points, we used statistical techniques to identify a set of 41 common mutation events that occurred repeatedly in multiple patients. These events appear to drive tumour formation and provide new opportunities for research into the origins of prostate cancer.
To reduce the overtreatment of prostate cancer in the short term, we applied machine learning techniques to merge the 41 common mutation events into a new signature that accurately predicts which patients have aggressive prostate cancer that needs urgent intervention and which may benefit from monitoring of their disease. If validated in future studies, this biomarker has the potential to improve survival and reduce side effects for hundreds of thousands of prostate cancer patients in North America each year. This is because overtreatment can lead to increased mortality due to bacterial infections from unnecessary biopsies and complications from surgery and radiotherapy. It will also prevent men from incorrectly choosing active surveillance when they have aggressive disease.
How was the catalogue of prostate cancer mutations used to come up with the new signature?
We used machine learning techniques to create the new signature. This means that we created algorithms that adaptively identify trends in the data that are more complex than would be identified by humans studying the data. These trends are converted into a statistical model that studies the genome of a prostate cancer patient and predicts the likelihood that their disease will be aggressive; similar to the way predictive text on smartphones improves the more that the user types on the device.
How will this signature be used to guide prostate cancer therapy in the future?
The next steps, which are now underway, are to validate this signature in additional patients to prove its clinical utility. We expect validation of the signature to take two to three years. If this is successful, it could be converted into a format that can be easily used in every hospital and doctor’s office, and implemented broadly across the healthcare system as new technologies develop.
The CPC-GENE project has been conducting intensive prostate cancer research for years. Can you say what the publication of this research means for the group as a milestone?
CPC-GENE is a national collaboration, involving groups in British Columbia, Ontario and Quebec. We would not have been able to form this excellent team without Movember Foundation, Prostate Cancer Canada, and OICR coming together to fund and support it. CPC-GENE has grown to become the largest prostate cancer genomics project in the world and has created an innovative, dynamic research team that is pushing the frontiers of our understanding of prostate cancer, while ensuring that each man gets exactly the therapy most needed. This study marks a key step in towards that mission.