Epigenomic reactivation screening to identify genes silenced by DNA hypermethylation in human cancer

Area of Science:

• Epigenetics
• Cancer Biology
• Molecular Oncology

Background:

• Promoter DNA hypermethylation is a critical epigenetic mechanism inactivating tumor suppressor genes in human cancers.
• Identifying genes silenced by DNA hypermethylation is crucial for understanding cancer development and progression.

Purpose of the Study:

• To review the epigenomic reactivation screening strategy for identifying novel tumor suppressor genes in cancer.
• To highlight recent studies utilizing this approach for gene discovery.

Main Methods:

• Epigenomic reactivation screening involves treating cancer cells with DNA methyltransferase and/or histone deacetylase inhibitors.
• Global gene expression analysis using microarrays identifies upregulated genes post-treatment.
• Complementary microarray analyses identify genes repressed in primary tumors.

Main Results:

• Epigenomic reactivation screening directly identifies genes with epigenetically altered expression.
• This strategy has proven effective in discovering novel tumor suppressor genes in various cancers.
• Recent studies demonstrate the utility and success of this screening approach.

Conclusions:

• Epigenomic reactivation screening is a powerful tool for discovering cancer-associated genes silenced by epigenetic modifications.
• This method offers advantages over direct methylation analysis by focusing on functional gene expression changes.
• The continued application of this strategy holds significant promise for advancing cancer therapeutics.