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Induction of tumors in mice by genomic hypomethylation.

Gaudet, François and Hodgson, J. Graeme and Eden, Amir and Jackson-Grusby, Laurie and Dausman, Jessica and Gray, Joe W. and Leonhardt, Heinrich and Jaenisch, Rudolf (2003):
Induction of tumors in mice by genomic hypomethylation.
300, In: Science (New York, N.Y.), (5618), pp. 489-92, ISSN 1095-9203, [Online-Edition: http://www.cardoso-lab.org/publications/Gaudet_2003.pdf],
[Article]

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.

Item Type: Article
Erschienen: 2003
Creators: Gaudet, François and Hodgson, J. Graeme and Eden, Amir and Jackson-Grusby, Laurie and Dausman, Jessica and Gray, Joe W. and Leonhardt, Heinrich and Jaenisch, Rudolf
Title: Induction of tumors in mice by genomic hypomethylation.
Language: English
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.

Journal or Publication Title: Science (New York, N.Y.)
Volume: 300
Number: 5618
Divisions: 10 Department of Biology
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10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 06 Mar 2010 07:33
Official URL: http://www.cardoso-lab.org/publications/Gaudet_2003.pdf
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