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Identification of Sleeping Beauty Transposon Insertions in Solid Tumors using Linker-mediated PCR
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Mouse models of cancer: Sleeping Beauty transposons for insertional mutagenesis screens and reverse genetic studies

Barbara R Tschida1, David A Largaespada1, Vincent W Keng2

  • 1Masonic 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.

Seminars in Cell & Developmental Biology
|January 29, 2014
PubMed

Insights

Forward genetic screens using Sleeping Beauty (SB) transposon technology identify cancer-promoting genes. This approach aids in understanding cancer genetics and developing new mouse models for targeted therapy research.

Area of Science:

  • Genetics
  • Cancer Biology
  • Genomics

Background:

  • Cancer's genetic complexity and heterogeneity present challenges for targeted therapy development.
  • Vast amounts of genomic data require interpretation to advance cancer understanding.
  • Distinguishing driver from passenger mutations is crucial for effective cancer treatment.

Purpose of the Study:

  • To explore the utility of Sleeping Beauty (SB) based insertional mutagenesis for unbiased forward genetic screens in cancer research.
  • To identify novel candidate cancer genes and drivers across multiple cancer types.
  • To assess the potential of SB technology for generating new mouse models for therapeutic testing.

Main Methods:

  • Utilizing Sleeping Beauty (SB) based insertional mutagenesis in mice for forward genetic screening.
  • Performing unbiased screens to identify genes driving various cancer types.
  • Developing new mouse models based on identified candidate mutations.

Main Results:

  • Identified hundreds of candidate cancer-promoting mutations through SB-based screens.
  • Demonstrated the effectiveness of SB technology in discovering potential cancer drivers.
  • Successfully modeled glioblastoma and liver cancer using SB technology.

Conclusions:

  • SB-based forward genetic screening is an effective strategy for cancer gene discovery.
  • The identified mutations and generated mouse models can facilitate further research and therapeutic testing.
  • SB technology offers a promising avenue for rapid generation of reverse genetic cancer models.
Keywords:
Cancer gene discoveryInsertional mutagenesisMouse modelsSleeping BeautyTransposable elements

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