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.