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UI findings indicate DNA methylation process may lead to oral cancer

than 8,000 deaths.

Cody had identified an oral cancer cell line that had lost expression of the tumor suppressor gene p16INK4A gene but in which the gene was still intact. Because the gene was still intact, the investigators knew that the cell line had not suffered any gross tumor suppressor gene deletion and that methylation might be to blame for the cancer.

To test their hypothesis, the researchers isolated DNA from normal human oral keratinocytes and from the cancer cell line.

"We found a really striking difference in the methylation patterns of cytosine," Domann said. "In the normal human oral keratinocytes that had p16 expression, we found there was virutally no cytosine methylation, and the cancer cells that lacked p16 expression were nearly completely methylated."

Domann and his research team plan to do additional methylation studies to screen other oral cancer cell lines.

"We think that this might be a general mechanism in oral cancers, as well as in other cancers, for inactivating this gene locus," Domann said.

P16INK4A is a broad-acting tumor suppressor gene. Its methylation, and its deletion and mutation can be found in various tumor types, Domann said.

Although Domann stressed that the clinically relevancy of his lab's findings is still years away, aberrant cytosine methylation eventually can be corrected. Ezymes in the cell, called DNA methyltransferase, mediate methylation.

"Any process that is mediated by an enzyme has the potential to be pharmacologically affected," Domann said. "Those enzymes can be targeted by drugs that are designed to inhibit the active sites for those enzymes."

The findings of Domann's research team appeared in a recent issue of the peer-reviewed European Journal of Cancer, Oral Oncology. Funding from the National Institutes of Health helped support this research.

In addition to Domann and Cody, the other researchers involved included Yuanhui Huang, Ph.D., currently a postdoctoral resear
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Contact: Jennifer Cronin
jennifer-cronin@uiowa.edu
319-335-9917
University of Iowa
4-Oct-1999


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