Mapping the Evolutionary Landscape of Pancreatic Cancer

This study uncovers the evolutionary dynamics of pancreatic ductal adenocarcinoma (PDAC), moving beyond traditional genomic descriptions to explore tumor development through phylogenetic and clonal analyses of 91 cases. Researchers identified no significant differences in the timing or number of driver mutations but found that high "truncal density"—a measure of accumulated mutations in the main tumor lineage—correlated with worse survival outcomes. Metastatic PDAC displayed diverse clonal patterns: polyclonal, monoclonal, or mixed, with polyclonality linked to advanced disease stages and prior treatment. In contrast, oligometastatic tumors were more likely monoclonal and harbored fewer driver mutations. These findings highlight the genomic variability in PDAC progression and introduce truncal density as a potential biomarker for prognosis, offering new perspectives for personalized cancer therapy.