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| Item Type: | Article |
|---|---|
| Title: | Induction of tumors in mice by genomic hypomethylation |
| Creators Name: | Gaudet, F., Hodgson, J.G., Eden, A., Jackson-Grusby, L., Dausman, J., Gray, J.W., 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 |
| Source: | Science |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 300 |
| Number: | 5618 |
| 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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