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

Nature communications 2019 Jul 22

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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.

Citation

Jonathan P Rennhack, Briana To, Matthew Swiatnicki, Caleb Dulak, Martin P Ogrodzinski, Yueqi Zhang, Caralynn Li, Evan Bylett, Christina Ross, Karol Szczepanek, William Hanrahan, Muthu Jayatissa, Sophia Y Lunt, Kent Hunter, Eran R Andrechek. Integrated analyses of murine breast cancer models reveal critical parallels with human disease. Nature communications. 2019 Jul 22;10(1):3261