Abstract:
:The DNA methylation pattern of a cell is exquisitely controlled during early development resulting in distinct methylation patterns. The tight control of DNA methylation is released in the cancer cell characterized by a reversal of methylation states. CpG island associated genes, in particular tumour suppressor or related genes, are often hypermethylated and this is associated with silencing of these genes. Therefore methylation is commonly convicted as a critical causal event in silencing this important class of genes in cancer. In this review, we argue that methylation is not the initial guilty party in triggering gene silencing in cancer, but that methylation of CpG islands is a consequence of prior gene silencing, similar to the role of methylation in maintaining the silencing of CpG island genes on the inactive X chromosome. We propose that gene silencing is the critical precursor in cancer, as it changes the dynamic interplay between de novo methylation and demethylation of the CpG island and tilts the balance to favour hypermethylation and chromatin inactivation.
journal_name
Oncogenejournal_title
Oncogeneauthors
Clark SJ,Melki Jdoi
10.1038/sj.onc.1205598subject
Has Abstractpub_date
2002-08-12 00:00:00pages
5380-7issue
35eissn
0950-9232issn
1476-5594journal_volume
21pub_type
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