Promoter hypermethylation patterns of p16, O-6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients

Aberrant promoter hypermethylation is common in head and neck cancer and ma y be useful as a marker for cancer cells. We examined whether cells with tu mor-specific aberrant DNA-methylation might be found in the saliva of affec ted patients. We tested 30 patients with primary head and neck tumors using methylation-specific PCR searching for promoter hypermethylation of the tu mor suppressor gene p16 (CDKN2A), the DNA repair gene O-6-methylguanine-DNA -methyltransferase (MGMT) and the putative metastasis suppressor gene death -associated protein kinase (DAP-K), Aberrant methylation of at least one of these genes was detected in 17 (56%) of 30 head and neck primary tumors; 1 4 (47%) of 30 at p16, 10 (33%) of 30 at Dap-K and 7 (23%) of 30 at MGMT, In 11 (65%) of 17 methylated primary tumors abnormal methylated DNA was detec ted in the matched saliva samples. Abnormal promoter methylation in saliva DNA was round in all tumor stages and more frequently in tumors located in the oral cavity, Moreover, none of the saliva from patients with methylatio n-negative tumors displayed methylation of any marker. Of 30 saliva samples from healthy control subjects (15 smokers and 15 nonsmokers), only one sam ple from a smoking. patient was positive for DNA methylation at two target genes. Detection of aberrant promoter hypermethylation patterns of cancer-r elated genes in saliva of head and cancer patients is feasible and may be p otentially useful for detecting and monitoring disease recurrence, Long-ter m longitudinal studies are needed to evaluate this approach for early detec tion of head and neck cancer in at-risk populations.