Characterization of genetic subclonal evolution in pancreatic cancer mouse models

Noushin Niknafs, Yi Zhong, John Alec Moral, Lance Zhang, Melody Xiaoshan Shao, April Lo, Alvin Makohon-Moore, Christine A. Iacobuzio-Donahue () and Rachel Karchin ()
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Noushin Niknafs: Johns Hopkins University
Yi Zhong: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
John Alec Moral: Memorial Sloan Kettering Cancer Center
Lance Zhang: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Melody Xiaoshan Shao: Johns Hopkins University
April Lo: Johns Hopkins University
Alvin Makohon-Moore: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
Christine A. Iacobuzio-Donahue: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
Rachel Karchin: Johns Hopkins University

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-13100-w

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