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CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future

Oncogene volume 21, pages 5427–5440 (2002)Cite this article

Abstract

We have come a long way since the first reports of the existence of aberrant DNA methylation in human cancer. Hypermethylation of CpG islands located in the promoter regions of tumor suppressor genes is now firmly established as an important mechanism for gene inactivation. CpG island hypermethylation has been described in almost every tumor type. Many cellular pathways are inactivated by this type of epigenetic lesion: DNA repair (hMLH1, MGMT), cell cycle (p16INK4a, p15INK4b, p14ARF), apoptosis (DAPK), cell adherence (CDH1, CDH13), detoxification (GSTP1), etc … However, we still know little of the mechanisms of aberrant methylation and why certain genes are selected over others. Hypermethylation is not an isolated layer of epigenetic control, but is linked to the other pieces of the puzzle such as methyl-binding proteins, DNA methyltransferases and histone deacetylase, but our understanding of the degree of specificity of these epigenetic layers in the silencing of specific tumor suppressor genes remains incomplete. The explosion of user-friendly technologies has given rise to a rapidly increasing list of hypermethylated genes. Careful functional and genetic studies are necessary to determine which hypermethylation events are truly relevant for human tumorigenesis. The development of CpG island hypermethylation profiles for every form of human tumors has yielded valuable pilot clinical data in monitoring and treating cancer patients based in our knowledge of DNA methylation. Basic and translational will both be needed in the near future to fully understand the mechanisms, roles and uses of CpG island hypermethylation in human cancer. The expectations are high.

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Acknowledgements

The work of my laboratory is sponsored by the Health Department of the Spanish Government, the I+D+I SAF 2001-0059 Grant and the International Rett Syndrome Association. I would like to thank Dr Esteban Ballestar and Dr Mario F Fraga for their critical reading of the manuscript. I apologize to all authors whose work on DNA methylation or whose favorite hypermethylated gene has not been mentioned due to space limitations.

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    Manel Esteller

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Esteller, M. CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene 21, 5427–5440 (2002). https://doi.org/10.1038/sj.onc.1205600

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