Jüri Reimand still remembers the moment his team spotted the pattern: in nearly every aggressive prostate tumor, hidden switches in the DNA were flipped, turning quiet genes into roaring engines of cancer growth. Their study, spanning nearly 1,000 tumors from nine countries, has uncovered powerful new clues about why some prostate cancers turn deadly while others remain harmless for decades. This isn’t just about mutations in well-known cancer genes—it’s about the overlooked corners of the genome, where silent changes can have life-or-death consequences.
Prostate cancer affects millions, but its behavior is wildly unpredictable. Some men live with slow-growing tumors their whole lives, while others face rapid spread and poor outcomes. The difference often lies in the genome. By analyzing whole-genome sequencing data, Reimand and his co-leader Joachim Weischenfeldt mapped a comprehensive catalog of genetic drivers, including ones never seen before. They found that 97% of tumors carry at least one known or potential cancer-driving alteration—proof that genetic changes are nearly universal in this disease.
One of the most surprising discoveries was a phenomenon called "enhancer hijacking." Normally, enhancers are genetic switches that control when and where genes turn on. But in some tumors, DNA rearrangements place these switches next to cancer-promoting genes, turning them on at the wrong time and place. The study found that enhancers linked to solute carrier genes—involved in moving molecules across cell membranes—are frequently hijacked, potentially fueling tumor growth.
Even more impactful, the team identified four distinct genomic subtypes of prostate cancer. Two of these subtypes are strongly linked to a higher risk of metastasis, offering a powerful tool for predicting which patients need aggressive treatment and which can avoid unnecessary interventions. In nearly 25% of tumors, the researchers found potential targets for existing cancer drugs, opening doors for personalized therapies. They also found key differences across ancestral groups—specific drivers were more common in men of African ancestry and linked to more aggressive disease, highlighting the need for diverse representation in genomic research.
These findings are part of a growing effort by the Pan Prostate Cancer Group, a global collaboration that has now gathered genomic and clinical data from about 2,000 patients. The goal is clear: to turn genetic insights into better outcomes. With further validation, these genomic subtypes could become standard tools in clinics, helping doctors tailor treatment to each patient’s tumor biology. As Reimand puts it, understanding these differences isn’t just academic—it’s the path to more precise, more humane care.