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A DNA transposon-based approach to validate oncogenic mutations in the mouse |
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| Authors: | 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 |
| Affiliation: | aWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, England; ;bThe Cancer Institute, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan; ;cDepartment of Anatomy and Cell Biology, University of Iowa, 100 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242-1109; and ;dInstitute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673 |
| 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. |
| Keywords: | cancer validation genetics genomics |