Authors
Peter A Jones, Peter W Laird
Publication date
1999/2
Source
Nature genetics
Volume
21
Issue
2
Pages
163-167
Publisher
Nature Publishing Group
Description
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.
Total citations
Scholar articles
PA Jones, PW Laird - Nature genetics, 1999