PT  - JOURNAL ARTICLE
AU  - Gaudet, François
AU  - Hodgson, J. Graeme
AU  - Eden, Amir
AU  - Jackson-Grusby, Laurie
AU  - Dausman, Jessica
AU  - Gray, Joe W.
AU  - Leonhardt, Heinrich
AU  - Jaenisch, Rudolf
TI  - Induction of Tumors in Mice by Genomic Hypomethylation
AID  - 10.1126/science.1083558
DP  - 2003 Apr 18
TA  - Science
PG  - 489--492
VI  - 300
IP  - 5618
4099  - http://science.sciencemag.org/content/300/5618/489.short
4100  - http://science.sciencemag.org/content/300/5618/489.full
SO  - Science2003 Apr 18; 300
AB  - 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.