Mouse Models of Breast Cancer Share Amplification and Deletion Events with Human Breast Cancer
- 464 Downloads
Breast tumor heterogeneity has been well documented through the use of multiplatform –omic studies in human tumors. However, there is no integrative database to capture the heterogeneity within mouse models of breast cancer. This project identifies genomic copy number alterations (CNAs) in 600 tumors across 27 major mouse models of breast cancer through the application of a predictive algorithm to publicly available gene expression data. It was found that despite the presence of strong oncogenic drivers in most mouse models, CNAs are extremely common but heterogeneous both between models and within models. Many mouse CNA events are largely conserved in human tumors and in the mouse we show that they are associated with secondary tumor characteristics such as tumor histology, metastasis, as well as enhanced oncogenic signaling. These data serve as an important resource in guiding investigators when choosing a mouse model to understand the gene copy number changes relevant to human breast cancer.
KeywordsCopy number variation Mouse model Breast cancer Gene expression Metastasis
We thank the members of the Andrechek laboratory for helpful discussions.
JR and EA collaborated on the study conception, design, and interpretation of results. BT provided histological coordination with CNA. HW provided the ACE analysis for many mouse models. JR performed all other experiments and drafted the manuscript. All authors have critically read, edited, and approved the final version of the manuscript.
Compliance with Ethical Standards
Conflict of Interest
The authors declare they have no conflict of interest.
This work was supported with NIH R01CA160514 to E.R. A and 1F99CA212221–01 to J.R.
- 26.Herschkowitz JI, Zhao W, Zhang M, Usary J, Murrow G, Edwards D, et al. Comparative oncogenomics identifies breast tumors enriched in functional tumor-initiating cells. Proc Natl Acad Sci U S A. 2012;109(8):2778–83.Google Scholar
- 28.Hollern DP, Andrechek E. A genomic analysis of mouse models of breast cancer reveals molecular features of mouse models and relationships to human breast cancer. Breast Cancer Res. 2014, 16(R59).Google Scholar
- 45.Andrechek ER. HER2/neu tumorigenesis and metastasis is regulated by E2F activator transcription factors. Oncogene. 2015;34(2):217–25.Google Scholar
- 47.Yuwanita I, Barnes D, Monterey MD, O'Reilly S, Andrechek ER. Increased metastasis with loss of E2F2 in myc-driven tumors. Oncotarget. 2015;6(35):38210–24.Google Scholar
- 48.Hollern DP, Honeysett J, Cardiff RD, Andrechek ER. The E2F transcription factors regulate tumor development and metastasis in a mouse model of metastatic breast cancer. Mol Cell Biol. 2014;34(17):3229–43.Google Scholar