Abstract
Promoter DNA hypermethylation is the key epigenetic mechanism by which tumor suppressor genes are inactivated in human cancer. The discovery of the importance of this mechanism has spurred the development of a number of approaches to identify genes silenced by DNA hypermethylation in cancer. One of the most useful of these approaches is an epigenomic reactivation screening strategy that combines treatment of cancer cells in vitro with DNA methyltransferase and/or histone deacetylase inhibitors, followed by global gene expression analysis using microarrays, to identify upregulated genes. This approach is most effective when complemented by microarray analyses to identify genes repressed in primary tumors. Epigenomic reactivation screening has a number of key advantages over direct analysis of cancer-associated DNA methylation changes; most notably, it directly identifies genes in which epigenetic changes lead to altered gene expression. An increasing number of studies have utilized epigenomic reactivation screening to discover novel tumor suppressor genes in cancer. The results of some of the most recent studies are highlighted in this review.
Original language | English (US) |
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Pages (from-to) | 231-241 |
Number of pages | 11 |
Journal | Current Opinion in Molecular Therapeutics |
Volume | 9 |
Issue number | 3 |
State | Published - Jun 2007 |
Externally published | Yes |
Keywords
- 5-Aza-2′-deoxycytidine
- Cancer
- DNA methylation
- Epigenetics
- HDAC inhibitor
- Microarray
- Tumor suppressor gene
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
- Pharmacology
- Drug Discovery
- Genetics(clinical)