Prostate Cancer Genomic Analysis Identifies Mutational Footprints Linked to Clinical Outcomes
A recent genomic analysis of nearly 1,000 prostate tumor samples has identified eight integrated mutational footprints (IMFs) that account for the majority of genetic alterations in prostate cancer genomes. Conducted by researchers including Joachim Weischenfeldt, PhD, from the University of Copenhagen, the study utilized whole-genome sequencing data from 959 primary prostate cancers with diverse histopathological stages and clinical outcomes. The analysis integrated multiple signature modalities, including single-base substitutions, insertion-deletions, copy number variants, and complex structural variants. These IMFs, which explain mutational processes in 85% of primary prostate cancer genomes, are primarily linked to hormone signaling, DNA replication and repair failures, and aging. The study found that four of these IMFs, present in 37% of primary tumors, were significantly associated with a shorter time to metastasis, while others predicted sensitivity to androgen receptor pathway inhibitors.
