A DNA transposon-based approach to validate oncogenic mutations in the mouse

Qin Su, Haydn M. Prosser, Lia S. Campos, Mariaestela Ortiz, Takuro Nakamura, Madhuri Warren, Adam J. Dupuy, Nancy A. Jenkins, Neal G. Copeland, Allan Bradley, Pentao Liu

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Large-scale cancer genome projects will soon be able to sequence many cancer genomes to comprehensively identify genetic changes in human cancer. Genome-wide association studies have also identified putative cancer associated loci. Functional validation of these genetic mutations in vivo is becoming a challenge. We describe here a DNA transposon-based platform that permits us to explore the oncogenic potential of genetic mutations in the mouse. Briefly, promoter-less human cancer gene cDNAs were first cloned into Sleeping Beauty (SB) transposons. DNA transposition in the mouse that carried both the transposons and the SB transposase made it possible for the cDNAs to be expressed from an appropriate endogenous genomic locus and in the relevant cell types for tumor development. Consequently, these mice developed a broad spectrum of tumors at very early postnatal stages. This technology thus complements the large-scale cancer genome projects.

Original languageEnglish (US)
Pages (from-to)19904-19909
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number50
DOIs
StatePublished - Dec 16 2008

Keywords

  • Cancer
  • Genetics
  • Genomics
  • Validation

ASJC Scopus subject areas

  • General

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