Whole-genome study reveals four forms of prostate cancer linked to disease progression
An international team of researchers, co-led by Joachim Weischenfeldt and Jüri Reimand at OICR, has identified four distinct genomic forms of prostate cancer, revealing new clues about why some tumours remain relatively slow growing while others are more likely to spread and become life-threatening. Published in Nature Communications, the study analysed whole-genome sequencing data from more than 1,000 men and provides one of the most comprehensive maps to date of the genetic changes that drive prostate cancer.
The researchers found that prostate cancer is not a single disease at the molecular level. Instead, tumours could be grouped into four genomic "oncotypes" defined by distinct oncogenic driver alterations. Importantly, two of these oncotypes were associated with poorer outcomes and a greater risk of disease progression, highlighting their potential value for future patient stratification and risk assessment.
"One of the biggest challenges in prostate cancer is understanding why some tumours remain manageable while others become aggressive and spread. By studying the complete genomes of more than 1,000 patients, we identified four distinct genomic forms of the disease and uncovered previously hidden cancer drivers. These insights bring us closer to a more precise biological understanding of prostate cancer and could help guide future strategies for patient stratification and treatment," said Joachim Weischenfeldt, senior author of the study and Group Leader at the Finsen Laboratory, Rigshospitalet, and the University of Copenhagen.
Beyond confirming known cancer drivers, the study uncovered previously unrecognised alterations in non-coding regions of the genome. These regions do not contain instructions for making proteins but play an important role in regulating gene activity. The researchers also identified examples of "enhancer hijacking", where structural variants reposition distal active enhancers, bringing oncogenes under the control of these enhancers and driving their expression.
Researchers from the Finsen Laboratory, at Rigshospitalet, and the Biotech Research and Innovation Centre, at the University of Copenhagen, contributed to the international Pan Prostate Cancer Group collaboration. The work forms part of a broader effort to understand the full spectrum of genomic alterations involved in prostate cancer and to build a more complete foundation for future precision medicine approaches.
The findings are not expected to change patient care immediately, and further validation will be needed before the newly identified oncotypes can be used in clinical practice. However, by providing a clearer picture of the biological differences between tumours, the research offers an important resource for scientists and clinicians seeking to improve the diagnosis, prognosis and treatment of prostate cancer in the years ahead.