Scientists Discover New Form of Prostate Cancer

A newly discovered hereditary cancer risk could change how doctors identify vulnerable families.

Researchers at the University of British Columbia have identified a previously unrecognized form of hereditary prostate cancer linked to a rare genetic mutation that can lead to aggressive disease at relatively young ages. The discovery could help doctors identify families with an inherited cancer risk and introduce earlier screening, potentially detecting tumors before they spread.

The new study, published in Cancer Discovery, connects this form of hereditary prostate cancer to inherited mutations in a gene called CDK12. After analyzing genetic data from more than 4,500 people with aggressive prostate cancer, researchers identified five unrelated men carrying these mutations. All five developed metastatic prostate cancer between ages 44 and 62.

A Hidden Genetic Cause of Aggressive Prostate Cancer

Scientists previously believed that harmful CDK12 mutations developed spontaneously within tumor cells rather than being inherited from a parent. To investigate whether inherited mutations were responsible for the cancers, researchers examined the patients’ tumors for a distinctive pattern of genetic changes associated with CDK12 dysfunction.

“The tumors provided us with a genetic signature that pointed directly back to CDK12,” said lead author Dr. Sofie Tolmeijer, a postdoctoral fellow in the Wyatt lab. “It gave us compelling evidence that these inherited mutations were playing a direct role in causing their cancer.”

“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, associate professor of urologic sciences at UBC and UBC President’s Excellence Chair in Precision Oncology. “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.”

A Rare Mutation With Implications for Families

Approximately 5 to 10 percent of cancers are associated with inherited genetic mutations, rather than changes that accumulate during a person’s lifetime. Among the best-known examples are BRCA1 and BRCA2 mutations, which increase the risk of breast, ovarian, pancreatic, and prostate cancers. Genetic testing for these mutations already helps guide cancer screening and preventive care.

Inherited CDK12 mutations appear considerably rarer. The researchers estimate that they occur in approximately one in 1,000 people with aggressive prostate cancer, potentially affecting hundreds of families worldwide. Identifying a carrier could allow relatives to undergo genetic testing and determine whether they share the mutation.

“While this mutation is extremely rare, the discovery could be lifesaving for the families who carry it,” said Dr. Tolmeijer. “Finding one person with an inherited mutation gives us the opportunity to identify other family members at risk and help them take action before cancer develops or spreads.”

Existing Genetic Tests Could Help Detect the Risk

The research team recommends considering CDK12 for inclusion in standard hereditary prostate cancer testing panels. Unlike genetic discoveries that require new diagnostic methods, CDK12 mutations can already be detected using existing clinical technology, potentially making expanded testing faster and less expensive to implement.

“One of the most exciting aspects of this discovery is that we already have the technology needed to act on it,” said Dr. Wyatt, who is also a senior research scientist at the Vancouver Prostate Centre and senior scientist at BC Cancer. “Adding CDK12 to existing genetic tests is relatively straightforward, which means this discovery could move from the research lab into clinical care much more quickly.”

The findings also raise questions about whether inherited CDK12 mutations contribute to ovarian cancer. Several affected men had family histories of ovarian cancer, and researchers identified an additional person with ovarian cancer who carried an inherited CDK12 mutation. That person’s tumor displayed the same characteristic genetic changes associated with CDK12 dysfunction. Further research is needed to establish whether the mutation increases ovarian cancer risk.

“With the right genetic testing and screening programs, we envision a future where no one who inherits one of these mutations dies from cancer,” said Dr. Wyatt.

Reference: “Germline CDK12 Variants in Aggressive Prostate Cancer” by Sofie H. Tolmeijer, Corinne Maurice-Dror, Shahneen Sandhu, Claire M. de la Calle, Christian Kollmannsberger, Mohamed Adil, Catherine K. Wang, Andrew J. Murtha, Gráinne Donnellan, Nielka P. van Erp, Niven Mehra, Michael S. Hofman, Arun A. Azad, Ian D. Davis, Andries M. Bergman, Wilbert Zwart, Kim van der Zande, Lesley Seymour, Peter C. Black, Vahid Akbari, Lilian Cordova, Peter M. Lansdorp, Steven J.M. Jones, Peter S. Nelson, Elena Castro, Kasmintan A. Schrader, Gavin Ha, Heather H. Cheng, Piet Ost, David Olmos, Kim N. Chi, Colin C. Pritchard and Alexander W. Wyatt, 18 September 2026, Cancer Discovery.
DOI: 10.1158/2159-8290.CD-26-0084

The study was supported by the Prostate Cancer Foundation, Terry Fox Research Institute, Canadian Cancer Society, Canadian Institutes of Health Research, Michael Smith Health Research BC, U.S. National Institutes of Health, BC Cancer Foundation and other funding partners.

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