Researchers announced on June 30 that a new study has identified specific DNA methylation patterns in prostate tumors that are closely associated with the aggressiveness of prostate cancer. The findings, published June 17 in the journal Cancer Discovery, could help clinicians better predict which cancers are likely to become lethal and tailor treatment accordingly.
Paul C. Boutros, PhD, MBA, professor and director at Sanford Burnham Prebys Medical Discovery Institute, led an international team that created a compendium of 3,001 multi-ancestry prostate methylomes. These included samples from normal tissue through localized disease to advanced metastatic cancer. Of these samples, 884 also had detailed genetic or RNA characterization.
The researchers found four recurring "methylation subtypes" across patients. One subtype was linked to slow-growing cancers typically associated with aging prostates; two were tied to moderately growing cancers rarely spreading beyond the prostate; and one subtype was almost exclusively present in lethal metastatic cases. Boutros said these methylation patterns were highly predictable across age groups, ancestries, and different genetic mutations: "Methylation was the way the cancer took the information from cancer genetics, patient lifestyle and other features and created a single signal that we could read," said Boutros. "That made it an ideal biomarker, and helped us learn what really makes prostate cancers so common, and so dangerous."
Takafumi Yamaguchi, bioinformatician at Sanford Burnham Prebys and co-lead author of the study, described the project as a multidisciplinary effort involving 22 institutions worldwide: "A study like this is a beautiful, complex dance. There were 22 separate institutions from around the world working together. We needed to find ways for cancer biologists and statisticians to talk with urologists, radiation oncologists and pathologists. Many of the technologies, and the AI and data science techniques we used didn't exist just 10 years ago, so there was a lot of learning for everyone!"
Boutros said next steps include working out how to bring this information into clinical practice: "First and most importantly, we now want to work out how to get this information into prostate cancer clinics to help patients and their caregivers get the best possible treatment." He also noted future research will test whether improving oxygen flow through light exercise might reduce aggressive cases.
