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Nat Genet. 1999 Feb;21(2):163-7.

Cancer epigenetics comes of age.

Author information

1
Department of Biochemistry and Molecular Biology, University of Southern California School of Medicine, The Norris Comprehensive Cancer Center, Los Angeles 90033, USA. jones_p@froggy.hsc.usc.edu

Abstract

The discovery of numerous hypermethylated promoters of tumour-suppressor genes, along with a better understanding of gene-silencing mechanisms, has moved DNA methylation from obscurity to recognition as an alternative mechanism of tumour-suppressor inactivation in cancer. Epigenetic events can also facilitate genetic damage, as illustrated by the increased mutagenicity of 5-methylcytosine and the silencing of the MLH1 mismatch repair gene by DNA methylation in colorectal tumours. We review here current mechanistic understanding of the role of DNA methylation in malignant transformation, and suggest Knudson's two-hit hypothesis should now be expanded to include epigenetic mechanisms of gene inactivation.

PMID:
9988266
DOI:
10.1038/5947
[Indexed for MEDLINE]

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