A DNA transposon-based approach to validate oncogenic mutations in the mouse.
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.
Su
Qin
Q
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, England.
Prosser
Haydn M
HM
Campos
Lia S
LS
Ortiz
Mariaestela
M
Nakamura
Takuro
T
Warren
Madhuri
M
Dupuy
Adam J
AJ
Jenkins
Nancy A
NA
Copeland
Neal G
NG
Bradley
Allan
A
Liu
Pentao
P
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis / Q000379:methods*; D004251:DNA Transposable Elements / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D005816:Genetic Complementation Test; D015894:Genome, Human; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D019895:Transposases / Q000235:genetics
D004251:DNA Transposable Elements; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D019895:Transposases; C494471:sleeping beauty transposase, human