The importance of epigenetic silencing of tumor-related genes is just coming to be appreciated by the scientific community. Also, the fields of DNA methylation and chromatin structure have merged with the realization that chromatin modification and DNA methylation are intimately linked. The focus up until now has been on DNA base changes and chromosomal losses. Gene silencing by abnormal chromatin structure and DNA methylation are increasingly being accepted as major contributors to human disease. Our review summarized this conceptual change in a rapidly evolving field.

  Does it describe a new discovery or a new methodology that's useful to others?

The paper points out the commonality of these silencing mechanisms and discusses how they are linked. It also provides a clinical link and suggests how DNA methylation can be used for detection and prognosis and how it can then be reversed by drug therapy. 

  Could you summarize the significance of your paper in layman's terms?

Genes commonly get mutated or lost in human cancers and this directly contributes to cancer formation. New research shows that perfectly good genes can get permanently switched off in cancer cells—they are there, but can't be used to make cells behave normally. We are beginning to work out what causes this silencing and are developing drugs that can turn genes back on again and hopefully make the cancer cells behave like normal cells once again. 

  How did you become involved in this research?

In 1980, my laboratory discovered that 5-azacytidine was a powerful inhibitor of DNA methylation in mammalian cells and that it was quite remarkable in its ability to switch genes on. Since that time we have been fascinated to determine how DNA methylation contributed to normal cell behavior and became deranged in human cancers.

Peter A. Jones, Ph.D., D.Sc.
Director, USC/Norris Comprehensive Cancer Center
Keck School of Medicine
University of Southern California
Los Angeles, CA, USA