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Updated: May 21, 2026
Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
De novo DNA methyltransferases: oncogenes, tumor suppressors, or both?
Agustin F Fernandez1, Covadonga Huidobro, Mario F Fraga
1Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain.
Abstract:
Aberrant promoter DNA hypermethylation of tumor suppressor genes is a hallmark of cancer. This alteration is largely dependent on the action of de novo DNA methyltransferases (DNMTs) early during tumor progression, which supports the oncogenic role for these enzymes. However, recent research has identified several inactivating mutations of de novo DNMTs in various types of tumor. In addition, it has been shown that loss of de novo DNA methylation activity at advanced tumor stages leads to the promoter DNA demethylation-dependent expression of specific oncogenes. These new data support the notion that de novo DNMTs also have an important role in the maintenance of DNA methylation and suggest that, in addition to acting as oncogenes, they also behave as tumor suppressors. This potential dual role might have clinical implications, as DNMTs are currently considered bona fide targets in cancer therapy.
Insights
De novo DNA methyltransferases (DNMTs) play a dual role in cancer, acting as oncogenes early in tumor development and tumor suppressors later. This challenges their current use as cancer therapy targets.
Area of Science:
- Molecular Biology
- Cancer Genetics
- Epigenetics
Background:
- Aberrant DNA hypermethylation of tumor suppressor genes is a key feature of cancer, primarily driven by de novo DNA methyltransferases (DNMTs).
- DNMTs are traditionally viewed as oncogenes due to their role in initiating hypermethylation during early tumor progression.
Purpose of the Study:
- To investigate the complex and potentially dual role of de novo DNMTs in cancer development.
- To explore the implications of DNMTs' dual function on their therapeutic targeting in cancer therapy.
Main Methods:
- Review of recent research on de novo DNMTs' function in various tumor types.
- Analysis of genetic alterations and their impact on DNMT activity and DNA methylation patterns.
- Examination of DNMTs' role in both gene hypermethylation and demethylation-dependent oncogene expression.
Main Results:
- Inactivating mutations in de novo DNMTs have been observed in several tumor types.
- Loss of DNMT activity in advanced tumors can lead to DNA demethylation and oncogene expression.
- These findings suggest de novo DNMTs can act as tumor suppressors by maintaining DNA methylation.
Conclusions:
- De novo DNMTs exhibit a dual role in cancer, functioning as both oncogenes and tumor suppressors.
- This dual role complicates the therapeutic targeting of DNMTs in cancer treatment.
- Further research is needed to fully understand and leverage the complex functions of DNMTs in cancer therapy.
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