Induction of tumors in mice by genomic hypomethylation

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

Research output: Contribution to journalArticle

1091 Citations (Scopus)

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
Externally publishedYes

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DNA
Methyltransferases
Neoplasms
Genome
Chromosomes, Human, Pair 15
Chromosomal Instability
T-Cell Lymphoma
Trisomy
Epigenomics
Carcinogenesis
Alleles
Parturition

ASJC Scopus subject areas

  • General

Cite this

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

Induction of tumors in mice by genomic hypomethylation. / Gaudet, François; Hodgson, J. Graeme; Eden, Amir; Jackson-Grusby, Laurie; Dausman, Jessica; Gray, Joe; Leonhardt, Heinrich; Jaenisch, Rudolf.

In: Science, Vol. 300, No. 5618, 18.04.2003, p. 489-492.

Research output: Contribution to journalArticle

Gaudet, F, Hodgson, JG, Eden, A, Jackson-Grusby, L, Dausman, J, Gray, J, Leonhardt, H & Jaenisch, R 2003, 'Induction of tumors in mice by genomic hypomethylation', Science, vol. 300, no. 5618, pp. 489-492. https://doi.org/10.1126/science.1083558
Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray J et al. Induction of tumors in mice by genomic hypomethylation. Science. 2003 Apr 18;300(5618):489-492. https://doi.org/10.1126/science.1083558
Gaudet, François ; Hodgson, J. Graeme ; Eden, Amir ; Jackson-Grusby, Laurie ; Dausman, Jessica ; Gray, Joe ; Leonhardt, Heinrich ; Jaenisch, Rudolf. / Induction of tumors in mice by genomic hypomethylation. In: Science. 2003 ; Vol. 300, No. 5618. pp. 489-492.
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