Integrated analyses of murine breast cancer models reveal critical parallels with human disease

Nat Commun. 2019 Jul 22;10(1):3261. doi: 10.1038/s41467-019-11236-3.

Abstract

Mouse models have an essential role in cancer research, yet little is known about how various models resemble human cancer at a genomic level. Here, we complete whole genome sequencing and transcriptome profiling of two widely used mouse models of breast cancer, MMTV-Neu and MMTV-PyMT. Through integrative in vitro and in vivo studies, we identify copy number alterations in key extracellular matrix proteins including collagen 1 type 1 alpha 1 (COL1A1) and chondroadherin (CHAD) that drive metastasis in these mouse models. In addition to copy number alterations, we observe a propensity of the tumors to modulate tyrosine kinase-mediated signaling through mutation of phosphatases such as PTPRH in the MMTV-PyMT mouse model. Mutation in PTPRH leads to increased phospho-EGFR levels and decreased latency. These findings underscore the importance of understanding the complete genomic landscape of a mouse model and illustrate the utility this has in understanding human cancers.

Publication types

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

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Collagen Type I / genetics
  • Collagen Type I, alpha 1 Chain
  • Disease Models, Animal*
  • Extracellular Matrix Proteins / genetics
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mammary Neoplasms, Animal / genetics*
  • Mammary Neoplasms, Experimental / genetics
  • Mice
  • Mutation

Substances

  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Extracellular Matrix Proteins
  • chondroadherin