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Nat Commun. 2019 Nov 28;10(1):5435. doi: 10.1038/s41467-019-13100-w.

Characterization of genetic subclonal evolution in pancreatic cancer mouse models.

Author information

1
Department of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, 21218, USA.
2
Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
3
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
4
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
5
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. iacobuzc@mskcc.org.
6
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. iacobuzc@mskcc.org.
7
David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. iacobuzc@mskcc.org.
8
Department of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, 21218, USA. karchin@jhu.edu.
9
Department of Oncology, Cancer Biology Program, Johns Hopkins Medical Institutions, Baltimore, MD, 21287, USA. karchin@jhu.edu.

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.

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