Publication Date:
2003-04-19
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gaudet, Francois -- Hodgson, J Graeme -- Eden, Amir -- Jackson-Grusby, Laurie -- Dausman, Jessica -- Gray, Joe W -- Leonhardt, Heinrich -- Jaenisch, Rudolf -- CA87869/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Apr 18;300(5618):489-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12702876" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Animals
;
Birth Weight
;
Cell Transformation, Neoplastic
;
*Chromosome Aberrations
;
Chromosomes, Mammalian/*genetics/physiology
;
DNA (Cytosine-5-)-Methyltransferase/genetics/metabolism
;
*DNA Methylation
;
Endogenous Retroviruses/genetics/physiology
;
Gene Expression
;
Gene Expression Regulation, Neoplastic
;
Gene Rearrangement
;
Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
;
Genes, myc
;
Heterozygote
;
Loss of Heterozygosity
;
Lymphoma, T-Cell/*genetics/pathology
;
Mice
;
Mice, Transgenic
;
Moloney murine leukemia virus/genetics/physiology
;
Trisomy
;
Virus Activation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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