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.