Induction of tumors in mice by genomic hypomethylation

François Gaudet, J. Graeme Hodgson, Amir Eden, Laurie Jackson-Grusby, Jessica Dausman, Joe W. Gray, Heinrich Leonhardt, Rudolf Jaenisch

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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.

Original languageEnglish (US)
Pages (from-to)489-492
Number of pages4
JournalScience
Volume300
Issue number5618
DOIs
StatePublished - Apr 18 2003

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Cite this

Gaudet, F., Hodgson, J. G., Eden, A., Jackson-Grusby, L., Dausman, J., Gray, J. W., Leonhardt, H., & Jaenisch, R. (2003). Induction of tumors in mice by genomic hypomethylation. Science, 300(5618), 489-492. https://doi.org/10.1126/science.1083558