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Characterization of genetic subclonal evolution in pancreatic cancer mouse models

Author

Listed:
  • Noushin Niknafs

    (Johns Hopkins University)

  • Yi Zhong

    (Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • John Alec Moral

    (Memorial Sloan Kettering Cancer Center)

  • Lance Zhang

    (Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
    Human Oncology and Pathogenesis Program, 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
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Christine A. Iacobuzio-Donahue

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center)

  • Rachel Karchin

    (Johns Hopkins University
    Cancer Biology Program, Johns Hopkins Medical Institutions)

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.

Suggested Citation

  • Noushin Niknafs & Yi Zhong & John Alec Moral & Lance Zhang & Melody Xiaoshan Shao & April Lo & Alvin Makohon-Moore & Christine A. Iacobuzio-Donahue & Rachel Karchin, 2019. "Characterization of genetic subclonal evolution in pancreatic cancer mouse models," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13100-w
    DOI: 10.1038/s41467-019-13100-w
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