UBC researchers have discovered a new and aggressive type of hereditary prostate cancer, the first associated with mutations in the gene CDK12. The finding, reported online in Cancer Discovery, a journal of the American Association for Cancer Research, could ultimately lead to genetic testing and early cancer detection interventions tailored specifically for such high-risk families.
Most cancers are due to mutations acquired during a person’s lifetime; however, 5–10% of all cases arise from an inherited genetic predisposition. BRCA1 and BRCA2 are the best-studied, with mutations that dramatically increase the risks of breast, ovarian, pancreatic & prostate cancers. The advent of testing for BRCA has revolutionized the landscape of breast cancer care. The list now may also include CDK12.
The UBC-led team analyzed genetic data from more than 4,500 men with aggressive prostate cancer and found five unrelated patients carrying inherited CDK12 mutations. All five developed metastatic prostate cancer between the ages of 44 and 62.
“What’s striking is that every patient we identified with this inherited mutation had already developed metastatic disease by the time they were diagnosed,” said senior author Dr. Alexander Wyatt. “The opportunity now is to identify these families earlier and give people the chance to benefit from enhanced screening, when there are still curative treatment options.”
Until now, scientists believed that harmful CDK12 mutations occurred only spontaneously in tumor cells. But the team confirmed inheritance by identifying a distinctive genetic fingerprint left behind when CDK12 stops working. “The tumors provided us with a genetic signature that pointed directly back to CDK12,” explained lead author Dr. Sofie Tolmeijer.
Though rare, affecting about one in every 1,000 people with aggressive prostate cancer, the mutation could impact hundreds of families worldwide.
“While this mutation is extremely rare, the discovery could be lifesaving for the families who carry it,” said Tolmeijer. “Finding one person with an inherited mutation allows us to identify other family members at risk and help them take action before cancer develops or spreads.”
These findings suggest that CDK12 should be included in routine panels for genetic testing of familial prostate cancer. In contrast to many new biomarkers that are detected using novel technology, CDK12 mutations can be identified with existing clinical technologies; thus, implementation is relatively easy.
“One of the most exciting aspects of this discovery is that we already have the technology needed to act on it,” Wyatt noted.
Intriguingly, the study also hints that inherited CDK12 mutations may raise risks for ovarian cancer, as several patients had family histories of the disease, and one ovarian cancer patient carried the same mutation.
Dr. Wyatt summed up the vision: “With the right genetic testing and screening programs, we envision a future where no one who inherits one of these mutations dies from cancer.”
This discovery not only expands the map of hereditary cancer but also underscores the power of combining genomics, clinical data, and international collaboration to uncover hidden risks and to give families a chance at prevention before cancer takes hold.
