Publication: genomic driver alterations in prostate cancer

“The molecular heterogeneity and clinical impact of genomic driver alterations in prostate cancer” is published in Nature Communications. Together with the Pan Prostate Cancer Group (PPCG), we analysed whole-genome sequencing data from 961 primary prostate cancers to systematically identify cancer driver alterations and study their clinical relevance. The study was co-led by Diogo Pellegrina, Daria Kiriy and Kevin Cheng as co-first authors, with Joachim Weischenfeldt (University of Copenhagen) and Jüri Reimand (OICR) leading it as part of the PPCG Drivers & Mutational Processes working group. Key findings:

97% of tumours carried at least one recurrent genomic alteration, which shows the value of looking beyond protein-coding mutations to structural variants, copy-number alterations and non-coding elements.
New candidate drivers and regulatory mechanisms, including enhancer hijacking involving solute carrier genes such as SLC30A4, which can activate oncogenes.
Several alterations were associated with metastatic disease. Integrating them defined four genomic oncotypes with distinct molecular and clinical features, two of them associated with higher metastatic risk.
Nearly one in four tumours carried alterations linked to potential targeted therapies.

The study complements our recent Nature paper on mutational processes in prostate cancer: that work examined the processes that leave characteristic mutation patterns in cancer genomes, while this one focuses on the alterations that may drive cancer and their clinical consequences. Thank you to the many researchers and clinicians across the consortium, to the patients who donated their samples and clinical data, and to CIHR for funding.