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Induction of tumors in mice by genomic hypomethylation

François Gaudet1, J Graeme Hodgson, Amir Eden

  • 1Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

Science (New York, N.Y.)
|April 19, 2003
PubMed

Insights

DNA hypomethylation, an epigenetic change, plays a causal role in cancer development. Reduced DNA methyltransferase 1 (Dnmt1) in mice led to genome-wide hypomethylation and aggressive T cell lymphomas.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Genetics

Background:

  • Genome-wide DNA hypomethylation is observed in human cancers.
  • Its role as a cause or consequence of tumorigenesis remains unclear.

Purpose of the Study:

  • To investigate the causal role of DNA hypomethylation in tumor formation.
  • To explore the link between hypomethylation and chromosomal instability.

Main Methods:

  • Generated mice with a hypomorphic DNA methyltransferase 1 (Dnmt1) allele.
  • Reduced Dnmt1 expression to 10% of wild-type levels, causing genome-wide hypomethylation.

Main Results:

  • Mutant mice exhibited runting at birth.
  • Developed aggressive T cell lymphomas by 4-8 months of age.
  • Lymphomas showed a high frequency of chromosome 15 trisomy.

Conclusions:

  • DNA hypomethylation plays a causal role in cancer development.
  • Hypomethylation may promote tumor formation by inducing chromosomal instability.

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