| Autor: |
Rennhack, Jonathan P., To, Briana, Swiatnicki, Matthew, Dulak, Caleb, Ogrodzinski, Martin P., Zhang, Yueqi, Li, Caralynn, Bylett, Evan, Ross, Christina, Szczepanek, Karol, Hanrahan, William, Jayatissa, Muthu, Lunt, Sophia Y., Hunter, Kent, Andrechek, Eran R. |
| Zdroj: |
Nature Communications; 7/22/2019, Vol. 10 Issue 1, pN.PAG-N.PAG, 1p |
| Abstrakt: |
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. Mouse models are an essential tool in breast cancer research. Here, the authors present the genomic and transcriptomic profiles of two widely used mouse models, revealing parallels with the human disease specifically with metastasis and treatment response. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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