Characterization of genetic subclonal evolution in pancreatic cancer mouse models

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Animals
  • Clonal Evolution / genetics
  • DNA Copy Number Variations / genetics
  • Disease Models, Animal
  • Evolution, Molecular
  • Mice
  • Mice, Transgenic
  • Mutation
  • Pancreatic Neoplasms / genetics*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Receptor, Transforming Growth Factor-beta Type II / genetics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Trp53 protein, mouse
  • Tumor Suppressor Protein p53
  • Receptor, Transforming Growth Factor-beta Type II
  • Tgfbr2 protein, mouse
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)