title: Induction of tumors in mice by genomic hypomethylation.
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.
authors.affiliation: Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: François
authors.initials: F
authors.lastname: Gaudet
authors.forename: J Graeme
authors.initials: JG
authors.lastname: Hodgson
authors.forename: Amir
authors.initials: A
authors.lastname: Eden
authors.forename: Laurie
authors.initials: L
authors.lastname: Jackson-Grusby
authors.forename: Jessica
authors.initials: J
authors.lastname: Dausman
authors.forename: Joe W
authors.initials: JW
authors.lastname: Gray
authors.forename: Heinrich
authors.initials: H
authors.lastname: Leonhardt
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
mesh_terms: D000483:Alleles; D000818:Animals; D001724:Birth Weight; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D033481:Chromosomes, Mammalian / Q000235:genetics* / Q000502:physiology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D020077:Endogenous Retroviruses / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016259:Genes, myc; D006579:Heterozygote; D019656:Loss of Heterozygosity; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000502:physiology; D014314:Trisomy; D014775:Virus Activation
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse