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A DNA transposon-based approach to validate oncogenic mutations in the mouse
Journal article   Open access   Peer reviewed

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, …
Proceedings of the National Academy of Sciences - PNAS, Vol.105(50), pp.19904-19909
12/16/2008
DOI: 10.1073/pnas.0807785105
PMCID: PMC2597691
PMID: 19064922
url
https://doi.org/10.1073/pnas.0807785105View
Published (Version of record) Open Access

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.
Biological Sciences Genetics Genomics cancer validation

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