Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients

S. L B Rosas, Wayne Martin Koch, M. D G Da Costa Carvalho, L. Wu, J. Califano, W. Westra, J. Jen, David Sidransky

Research output: Contribution to journalArticle

Abstract

Aberrant promoter hypermethylation is common in head and neck cancer and may be useful as a marker for cancer cells. We examined whether cells with tumor-specific aberrant DNA-methylation might be found in the saliva of affected patients. We tested 30 patients with primary head and neck tumors using methylation-specific PCR searching for promoter hypermethylation of the tumor suppressor gene p16 (CDKN2A), the DNA repair gene O6-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; 14 (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 detected in the matched saliva samples. Abnormal promoter methylation in saliva DNA was found in all tumor stages and more frequently in tumors located in the oral cavity. Moreover, none of the saliva from patients with methylation-negative tumors displayed methylation of any marker. Of 30 saliva samples from healthy control subjects (15 smokers and 15 nonsmokers), only one sample from a smoking patient was positive for DNA methylation at two target genes. Detection of aberrant promoter hypermethylation patterns of cancer-related genes in saliva of head and cancer patients is feasible and may be potentially useful for detecting and monitoring disease recurrence. Long-term longitudinal studies are needed to evaluate this approach for early detection of head and neck cancer in at-risk populations.

Original languageEnglish (US)
Pages (from-to)939-942
Number of pages4
JournalCancer Research
Volume61
Issue number3
StatePublished - 2001

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Death-Associated Protein Kinases
Methyltransferases
Head and Neck Neoplasms
Saliva
Methylation
DNA
Neoplasms
DNA Methylation
Tumor Suppressor Genes
Neck
Head
Genes
O-(6)-methylguanine
Neoplasm Genes
Early Detection of Cancer
DNA Repair
Longitudinal Studies
Mouth
Healthy Volunteers
Smoking

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients. / Rosas, S. L B; Koch, Wayne Martin; Da Costa Carvalho, M. D G; Wu, L.; Califano, J.; Westra, W.; Jen, J.; Sidransky, David.

In: Cancer Research, Vol. 61, No. 3, 2001, p. 939-942.

Research output: Contribution to journalArticle

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abstract = "Aberrant promoter hypermethylation is common in head and neck cancer and may be useful as a marker for cancer cells. We examined whether cells with tumor-specific aberrant DNA-methylation might be found in the saliva of affected patients. We tested 30 patients with primary head and neck tumors using methylation-specific PCR searching for promoter hypermethylation of the tumor suppressor gene p16 (CDKN2A), the DNA repair gene O6-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; 14 (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 detected in the matched saliva samples. Abnormal promoter methylation in saliva DNA was found in all tumor stages and more frequently in tumors located in the oral cavity. Moreover, none of the saliva from patients with methylation-negative tumors displayed methylation of any marker. Of 30 saliva samples from healthy control subjects (15 smokers and 15 nonsmokers), only one sample from a smoking patient was positive for DNA methylation at two target genes. Detection of aberrant promoter hypermethylation patterns of cancer-related genes in saliva of head and cancer patients is feasible and may be potentially useful for detecting and monitoring disease recurrence. Long-term longitudinal studies are needed to evaluate this approach for early detection of head and neck cancer in at-risk populations.",
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