Understanding prostate cancer

Prostate cancer, the most common internal cancer in men, has been a long-standing puzzle due to its varying aggression levels and detection difficulty. A new study in Cancer Discovery, co-led by Professors Niall Corcoran and Chris Hovens of the University of Melbourne, has made significant strides in understanding the disease. The team conducted the largest whole genome analysis of a single cancer type, examining 666 prostate cancer genomes, ranging from mild to aggressive forms.

Three Melbourne Bioinformatics researchers, Chol-Hee Jung, Prof Daniel Park, and Prof Bernie Pope, were part of the team which catalogued 223 mutations, both inherited and somatic, that are responsible for prostate tumour development. (Peter Georgeson and Andrew Lonie both worked at Melbourne Bioinformatics during their time on the project.) Over a third of these mutations are undetectable by standard genetic tests, suggesting new diagnostic pathways. The team also identified 11 clusters of germline genetic variations, or driver quantitative trait loci (dQTLs), that influence tumour expression. Some of these dQTLs are active across different cancer types, and the data suggests there are at least 314 dQTLs yet to be discovered.

The researchers also used their data to trace the evolutionary history of the prostate tumours in their sample. They found that the differences in tumour aggression are different stages of the same disease, with slow-growing tumours lacking specific mutations. This research not only helps explain the complexities of prostate cancer but also holds promise for better detection and treatment of aggressive forms.

Yamaguchi, T.N., et al., 2025. The Germline and Somatic Origins of Prostate Cancer Heterogeneity. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-23-0882