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Int J Mol Sci. 2020 Feb 10;21(3). pii: E1172. doi: 10.3390/ijms21031172.

Transposon Insertion Mutagenesis in Mice for Modeling Human Cancers: Critical Insights Gained and New Opportunities.

Author information

1
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
2
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
3
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
4
Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.

Abstract

Transposon mutagenesis has been used to model many types of human cancer in mice, leading to the discovery of novel cancer genes and insights into the mechanism of tumorigenesis. For this review, we identified over twenty types of human cancer that have been modeled in the mouse using Sleeping Beauty and piggyBac transposon insertion mutagenesis. We examine several specific biological insights that have been gained and describe opportunities for continued research. Specifically, we review studies with a focus on understanding metastasis, therapy resistance, and tumor cell of origin. Additionally, we propose further uses of transposon-based models to identify rarely mutated driver genes across many cancers, understand additional mechanisms of drug resistance and metastasis, and define personalized therapies for cancer patients with obesity as a comorbidity.

KEYWORDS:

animal modeling; cancer; transposon screen

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