Characterization of genetic subclonal evolution in pancreatic cancer mouse models

The KPC mouse model, driven by the Kras and Trp53 transgenes, is well regarded for faithful recapitulation of human pancreatic cancer biology. However, the extent that this model recapitulates the subclonal evolution of this tumor type is unknown. Here we report evidence of continuing subclonal evolution after tumor initiation that largely reflect copy number alterations that target cellular processes of established significance in human pancreatic cancer. The evolutionary trajectories of the mouse tumors show both linear and branching patterns as well as clonal mixing. We propose the KPC model and derivatives have unexplored utility as a functional system to model the mechanisms and modifiers of tumor evolution. In pancreatic cancer the Kras and Trp53 transgene driven KPC mouse model is used to experimentally study disease processes. Here, the authors analyse tumour evolution within the KPC model, finding both linear and branched evolution and highlighting the utility of this model in mechanistic research of tumour evolution.