Induction of tumors in mice by genomic hypomethylation - PubMed (original) (raw)

. 2003 Apr 18;300(5618):489-92.

doi: 10.1126/science.1083558.

Affiliations

• PMID: 12702876
• DOI: 10.1126/science.1083558

Induction of tumors in mice by genomic hypomethylation

François Gaudet et al. Science. 2003.

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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Comment in

• Cancer. An unstable liaison.
  Lengauer C. Lengauer C. Science. 2003 Apr 18;300(5618):442-3. doi: 10.1126/science.1084468. Science. 2003. PMID: 12702865 No abstract available.
• Comment on "Chromosomal instability and tumors promoted by DNA hypomethylation" and "Induction of tumors in nice by genomic hypomethylation".
  Yang AS, Estecio MR, Garcia-Manero G, Kantarjian HM, Issa JP. Yang AS, et al. Science. 2003 Nov 14;302(5648):1153; author reply 1153. doi: 10.1126/science.302.5648.1153a. Science. 2003. PMID: 14615517 No abstract available.

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