Mouse models of cancer: Sleeping Beauty transposons for insertional mutagenesis screens and reverse genetic studies.
The genetic complexity and heterogeneity of cancer has posed a problem in designing rationally targeted therapies effective in a large proportion of human cancer. Genomic characterization of many cancer types has provided a staggering amount of data that needs to be interpreted to further our understanding of this disease. Forward genetic screening in mice using Sleeping Beauty (SB) based insertional mutagenesis is an effective method for candidate cancer gene discovery that can aid in distinguishing driver from passenger mutations in human cancer. This system has been adapted for unbiased screens to identify drivers of multiple cancer types. These screens have already identified hundreds of candidate cancer-promoting mutations. These can be used to develop new mouse models for further study, which may prove useful for therapeutic testing. SB technology may also hold the key for rapid generation of reverse genetic mouse models of cancer, and has already been used to model glioblastoma and liver cancer.
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Barbara R
BR
Tschida
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
David A
DA
Largaespada
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. Electronic address: vincent.keng@polyu.edu.hk.
Vincent W
VW
Keng
D000818:Animals; D004251:DNA Transposable Elements; D052138:Genes, Neoplasm; D006801:Humans; D008822:Mice, Transgenic; D016296:Mutagenesis; D016254:Mutagenesis, Insertional; D009374:Neoplasms, Experimental / Q000235:genetics*; D059386:Reverse Genetics; D019895:Transposases / Q000235:genetics
D004251:DNA Transposable Elements; D019895:Transposases; C494471:sleeping beauty transposase, human
Cancer gene discovery; Insertional mutagenesis; Mouse models; Sleeping Beauty; Transposable elements