July 19, 2006
In 1983, scientists published for the first time that a distinguishing feature of some human cancers is a small subset of their genes are “hypomethylated” compared to normal cells. This led to the discovery that genes can be turned on or off not only by sequence altering mutations but decreased methylation of their cytosine and adenosine residues, particularly in their transcription activating “promoter” region. As researchers dug deeper into this phenomenon, they determined that the opposite also can be true. Gene expression can be controlled by hypermethylation of these same residues. Today, research into the DNA methylation of tumor cells continues to provide promising biochemical grist in the search for targeted cancer treatments. In the June issue of the journal Archives of Otolaryngology/ Head and Neck Surgery, a team of NIDCR grantees and colleagues take a closer look in head and neck cancer at the role of DNA methylation and gene copy number (a laboratory term for the number of copies of particular gene within the DNA of a cell). Monitoring the methylation status and copy number of 22 recognized cancer-related genes in six distinct squamous cell carcinoma cell lines, they found epigenetic modifications in methylation clearly play a role in the onset and/or progression of this common head and neck cancer. In some cell lines, they found hypermethylation in the promoter region of several tumor suppressor genes completely abrogated their normal function.