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

doi:10.1126/science.1083558

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1248 Scopus citations

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 language	American English
Pages (from-to)	489-492
Number of pages	4
Journal	Science
Volume	300
Issue number	5618
DOIs	https://doi.org/10.1126/science.1083558
State	Published - 18 Apr 2003
Externally published	Yes

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10.1126/science.1083558

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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.",

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AU - Eden, Amir

AU - Jackson-Grusby, Laurie

AU - Dausman, Jessica

AU - Gray, Joe W.

AU - Leonhardt, Heinrich

AU - Jaenisch, Rudolf

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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.

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Induction of tumors in mice by genomic hypomethylation

Abstract

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