Tumor-suppressor gene promoter hypermethylation in saliva of head and neck cancer patients

Ovchinnikov, Dmitry A., Cooper, Matthew A., Pandit, Pratibala, Coman, William B., Cooper-White, Justin J., Keith, Patricia, Wolvetang, Ernst J., Slowey, Paul D., & Punyadeera, Chamindie (2012) Tumor-suppressor gene promoter hypermethylation in saliva of head and neck cancer patients. Translational Oncology, 5(5), pp. 321-326.

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Abstract

Head and neck squamous cell carcinoma (HNSCC) accounts for a bulk of the oral and laryngeal cancers, the majority (70%) of which are associated with smoking and excessive drinking, major known risk factors for the development of HNSCC. In contrast to reports that suggest an inverse relationship between smoking and global DNA CpG methylation, hypermethylation of promoters of a number of genes was detected in saliva collected from patients with HNSCC. Using a sensitive methylation-specific polymerase chain reaction (MSP) assay to determine specific methylation events in the promoters of RASSF1A, DAPK1, and p16 genes, we demonstrate that we can detect tumor presence with an overall accuracy of 81% in the DNA isolated from saliva of patients with HNSCC (n = 143) when compared with the DNA isolated from the saliva of healthy nonsmoker controls (n = 31). The specificity for this MSP panel was 87% and the sensitivity was 80%(with a Fisher exact test P < .0001). In addition, the test panel performed extremely well in the detection of the early stages of HNSCCs, with a sensitivity of 94% and a specificity of 87%, and a high. concordance value of 0.8, indicating an excellent overall agreement between the presence of HNSCC and a positive MSP panel result. In conclusion, we demonstrate that the promoter methylation of RASSF1A, DAPK1, and p16 MSP panel is useful in detecting hypermethylation events in a noninvasive manner in patients with HNSCC.

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ID Code: 77928
Item Type: Journal Article
Refereed: Yes
Additional Information: Times Cited: 9
Ovchinnikov, Dmitry A. Cooper, Matthew A. Pandit, Pratibala Coman, William B. Cooper-White, Justin J. Keith, Patricia Wolvetang, Ernst J. Slowey, Paul D. Punyadeera, Chamindie
Queensland Government Smart Futures Fellowship Program (QGSFF); Collaborative Industry Engagement Fund University of Queensland (UQCIEF); University of Queensland New Staff Research Funds [UQNSRSF 601252]
The authors acknowledge the financial support of the Queensland Government Smart Futures Fellowship Program (QGSFF), Collaborative Industry Engagement Fund University of Queensland (UQCIEF), and the University of Queensland New Staff Research Funds (UQNSRSF 601252). The authors declare no conflict of interest.
Keywords: squamous-cell carcinoma, aberrant methylation, lung-cancer, oral-cancer, dna, p16(ink4a), hypomethylation, association, smoking, profile
DOI: 10.1593/tlo.12232
ISSN: 1936-5233
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Neoplasia Press, Inc.
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Deposited On: 22 Oct 2014 02:49
Last Modified: 23 Oct 2014 03:42

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