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Induction of tumors in mice by genomic hypomethylation

Item Type:Article
Title:Induction of tumors in mice by genomic hypomethylation
Creators Name:Gaudet, F. and Hodgson, J.G. and Eden, A. and Jackson-Grusby, L. and Dausman, J. and Gray, J.W. and Leonhardt, H. and Jaenisch, R.
Abstract:Genome-wide DNA hypomethylation occurs in many human cancers, but whether this epigenetic change is a cause or consequence of tumorigenesis has been unclear. To explore this phenomenon, we generated mice carrying a hypomorphic DNA methyltransferase 1 (Dnmt1) allele, which reduces Dnmt1 expression to 10% of wild-type levels and results in substantial genome-wide hypomethylation in all tissues. The mutant mice were runted at birth, and at 4 to 8 months of age they developed aggressive T cell lymphomas that displayed a high frequency of chromosome 15 trisomy. These results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability.
Keywords:Alleles, Birth Weight, Neoplastic Cell Transformation, Chromosome Aberrations, Mammalian Chromosomes, DNA (Cytosine-5-)-Methyltransferase, DNA Methylation, Endogenous Retroviruses, Gene Expression, Neoplastic Gene Expression Regulation, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor Gene Rearrangement, myc Genes, Heterozygote, Loss of Heterozygosity, T-Cell Lymphoma, Moloney Murine Leukemia Virus, Trisomy, Virus Activation, Animals, Mice
Publisher:American Association for the Advancement of Science
Page Range:489-492
Date:18 April 2003
Official Publication:https://doi.org/10.1126/science.1083558
PubMed:View item in PubMed

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