Integrated signatures define mutational processes in prostate cancer.

Integrated mutational signatures in prostate cancer reveal eight key footprints explaining 85% of genomes and link to clinical outcomes.

• Why it matters: Understanding the mutational processes underlying prostate cancer is crucial for improving risk assessment and personalized treatment, yet these processes remain incompletely characterized.
• What they did: The study analyzed 959 prostate cancer genomes using de novo extraction of various mutational signatures, including single-base substitutions, insertions-deletions, copy-number changes, and complex structural variants, to identify eight integrated mutational footprints.
• The result: These IMFs, influenced by regional genomic biases, were associated with faster metastasis and predicted sensitivity to androgen receptor inhibitors, offering new avenues for risk stratification and targeted therapy.