UI findings indicate DNA methylation process may lead to oral cancer

IOWA CITY, Iowa--Just like a light switch, a process known as cytosine methylation can turn off expression of tumor suppressor genes and lead to oral cancer, according to University of Iowa Health Care research findings.

"During cancer development, the normal control of cytosine methylation is lost, and DNA can become aberrantly methylated," explained Frederick Domann, Ph.D., UI associate professor of radiology. "When this happens to a tumor suppressor gene, it switches off its expression and contributes to cancer progression."

For some time now, cancer researchers have focused on tumor suppressor genes in an attempt to answer the question of how cancer grows and spreads. When they work properly, tumor suppressor genes do just what their name suggests: They suppress cancer. However, if something disrupts the genes, the cancer grows and stretches into other areas of the body.

Classical genetics has shown that mutations and deletions of these tumor suppressor genes contribute to malignancy. However, another mechanism, DNA methylation, can inactivate tumor gene expression as well, Domann said. This methylation phenomenon is the focus of Domann's lab investigations. Methylation is the addition of single carbon atoms to specific target sites within the DNA.

Cytosine, one of the four nucleotides in DNA, is the only base that can be methylated normally by a cell's enzymatic machinery. Cytosine is normally methylated in cells at certain positions and not others. Carcinogenesis alters the pattern of cytosine methylation, which contributes to altered patterns of gene expression in cancer.

Based on the interest of one of his then post-doctoral fellows, D. Thane Cody II, M.D., currently assistant professor of surgery at Southern Illinois University, Domann and his team began investigating whether aberrant methylation contributed to oral cancer tumors. There were more than 28,000 news cases of oral cancer in the United States in 1995, resulting in more

Contact: Jennifer Cronin
University of Iowa

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