RT Journal Article SR Electronic T1 Induction of Tumors in Mice by Genomic Hypomethylation JF Science JO Science FD American Association for the Advancement of Science SP 489 OP 492 DO 10.1126/science.1083558 VO 300 IS 5618 A1 Gaudet, François A1 Hodgson, J. Graeme A1 Eden, Amir A1 Jackson-Grusby, Laurie A1 Dausman, Jessica A1 Gray, Joe W. A1 Leonhardt, Heinrich A1 Jaenisch, Rudolf YR 2003 UL http://science.sciencemag.org/content/300/5618/489.abstract 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.