Abstract

The Sleeping Beauty (SB) transposon insertional mutagenesis system offers a streamlined approach to identify genetic drivers of cancer. With a relatively random insertion profile, SB is uniquely positioned for conducting unbiased forward genetic screens. Indeed, SB mouse models of cancer have revealed insights into the genetics of tumorigenesis. In this review, we highlight experiments that have exploited the SB system to interrogate the genetics of cancer in distinct biological contexts. We also propose experimental designs that could further our understanding of the relationship between tumor microenvironment and tumor progression.

Highlights

  • We propose experimental designs that could further our understanding of the relationship between tumor microenvironment and tumor progression

  • Sleeping Beauty (SB) is a two-part DNA transposon system that has become an integral tool in identifying genetic drivers of cancers in mouse models

  • SB-induced cancer models have led to the discovery of novel cancer genes while comparative genomics have demonstrated the relevance of these models to human disease [1,2,3,4,5,6,7,8]

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Summary

Frontiers in Oncology

Mouse Models of Cancer: Microenvironmental Influences on Cancer Genetics. The Sleeping Beauty (SB) transposon insertional mutagenesis system offers a streamlined approach to identify genetic drivers of cancer. With a relatively random insertion profile, SB is uniquely positioned for conducting unbiased forward genetic screens. SB mouse models of cancer have revealed insights into the genetics of tumorigenesis. We highlight experiments that have exploited the SB system to interrogate the genetics of cancer in distinct biological contexts. We propose experimental designs that could further our understanding of the relationship between tumor microenvironment and tumor progression

UTILIZATION OF SLEEPING BEAUTY TO MODEL TUMOR FORMATION IN MICE
SB Origins and Optimization for Forward Genetic Screens
Regulation of the SB Machinery
Other Integrating Vector Systems
Interpreting SB Data
Gene mutated
SENSITIZING MUTATIONS IN SB MOUSE MODELS
Colorectal Disease
OTHER FACTORS INFLUENCING TUMOR DEVELOPMENT IN SB MODELS
Therapeutic Interventions
Environmental Exposures
Sex Bias
Immune Function
THE FUTURE OF SB MUTAGENESIS SCREENS
Therapeutic Interventions and Environmental Exposures
Inherent Traits
Findings
Genetics of Metastasis

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