3 Citations (Scopus)

Abstract

Introduction The relevance of DNA methylation of O6-methylguanine-DNA methyltransferase (MGMT) in relation to several cancers and other disorders has been extensively explored in several cancer types. Aims To ascertain the significance of DNA methylation of MGMT promoter in oral squamous cell carcinoma (OSCC), we undertook a study to a) analyse the methylation patterns of MGMT gene promoter in afflicted and normal population of coastal Karnataka, b) determine the expression status of MGMT in oral cancer cell lines (CAL-27 and SCC-4) and its relationship to DNA methylation and c) performed a meta-analysis of the published data. Methods Bisulfite sequencing of MGMT promoter region was performed on non-malignant/malignant oral samples, and oral cancer cell lines, followed by gene expression studies. Further, using a systematic search, 1024 publications were retrieved from PubMed, Scopus, Google Scholar and Web of Science and 23 relevant articles were reviewed. Results Significant association of MGMT promoter methylation with OSCC (p < 0.0001) was observed in the case-control study. The studies chosen for meta-analysis showed predictive significance of MGMT gene promoter. Overall, we obtained a statistically significant (p < 0.0001) association for both sensitivity and specificity of MGMT DNA promoter methylation in oral cancer cases without publication bias. Gene expression was significantly elevated in both oral cancer cell lines (p < 0.03) after treatment with a demethylating agent (5-Aza-2′-deoxycytidine). Conclusion DNA promoter hypermethylation and gene expression of MGMT may associate with recursive mutagenesis and is a promising biomarker for OSCC prediction. Studies suggest further validation in large distinct cohorts to facilitate translation to clinics.

Original languageEnglish
Pages (from-to)197-208
Number of pages12
JournalArchives of Oral Biology
Volume80
DOIs
Publication statusPublished - 01-08-2017

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Methyltransferases
DNA Methylation
Meta-Analysis
Carcinoma
DNA
Mouth Neoplasms
Population
Squamous Cell Carcinoma
decitabine
Gene Expression
Cell Line
Methylation
Publication Bias
DNA Sequence Analysis
PubMed
Genetic Promoter Regions
Mutagenesis
Genes
Publications
Case-Control Studies

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology
  • Dentistry(all)
  • Cell Biology

Cite this

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title = "Promoter methylation of MGMT in oral carcinoma: A population-based study and meta-analysis",
abstract = "Introduction The relevance of DNA methylation of O6-methylguanine-DNA methyltransferase (MGMT) in relation to several cancers and other disorders has been extensively explored in several cancer types. Aims To ascertain the significance of DNA methylation of MGMT promoter in oral squamous cell carcinoma (OSCC), we undertook a study to a) analyse the methylation patterns of MGMT gene promoter in afflicted and normal population of coastal Karnataka, b) determine the expression status of MGMT in oral cancer cell lines (CAL-27 and SCC-4) and its relationship to DNA methylation and c) performed a meta-analysis of the published data. Methods Bisulfite sequencing of MGMT promoter region was performed on non-malignant/malignant oral samples, and oral cancer cell lines, followed by gene expression studies. Further, using a systematic search, 1024 publications were retrieved from PubMed, Scopus, Google Scholar and Web of Science and 23 relevant articles were reviewed. Results Significant association of MGMT promoter methylation with OSCC (p < 0.0001) was observed in the case-control study. The studies chosen for meta-analysis showed predictive significance of MGMT gene promoter. Overall, we obtained a statistically significant (p < 0.0001) association for both sensitivity and specificity of MGMT DNA promoter methylation in oral cancer cases without publication bias. Gene expression was significantly elevated in both oral cancer cell lines (p < 0.03) after treatment with a demethylating agent (5-Aza-2′-deoxycytidine). Conclusion DNA promoter hypermethylation and gene expression of MGMT may associate with recursive mutagenesis and is a promising biomarker for OSCC prediction. Studies suggest further validation in large distinct cohorts to facilitate translation to clinics.",
author = "Chinchu Jayaprakash and Raghu Radhakrishnan and Satadru Ray and Kapaettu Satyamoorthy",
year = "2017",
month = "8",
day = "1",
doi = "10.1016/j.archoralbio.2017.04.006",
language = "English",
volume = "80",
pages = "197--208",
journal = "Archives of Oral Biology",
issn = "0003-9969",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Promoter methylation of MGMT in oral carcinoma

T2 - A population-based study and meta-analysis

AU - Jayaprakash, Chinchu

AU - Radhakrishnan, Raghu

AU - Ray, Satadru

AU - Satyamoorthy, Kapaettu

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Introduction The relevance of DNA methylation of O6-methylguanine-DNA methyltransferase (MGMT) in relation to several cancers and other disorders has been extensively explored in several cancer types. Aims To ascertain the significance of DNA methylation of MGMT promoter in oral squamous cell carcinoma (OSCC), we undertook a study to a) analyse the methylation patterns of MGMT gene promoter in afflicted and normal population of coastal Karnataka, b) determine the expression status of MGMT in oral cancer cell lines (CAL-27 and SCC-4) and its relationship to DNA methylation and c) performed a meta-analysis of the published data. Methods Bisulfite sequencing of MGMT promoter region was performed on non-malignant/malignant oral samples, and oral cancer cell lines, followed by gene expression studies. Further, using a systematic search, 1024 publications were retrieved from PubMed, Scopus, Google Scholar and Web of Science and 23 relevant articles were reviewed. Results Significant association of MGMT promoter methylation with OSCC (p < 0.0001) was observed in the case-control study. The studies chosen for meta-analysis showed predictive significance of MGMT gene promoter. Overall, we obtained a statistically significant (p < 0.0001) association for both sensitivity and specificity of MGMT DNA promoter methylation in oral cancer cases without publication bias. Gene expression was significantly elevated in both oral cancer cell lines (p < 0.03) after treatment with a demethylating agent (5-Aza-2′-deoxycytidine). Conclusion DNA promoter hypermethylation and gene expression of MGMT may associate with recursive mutagenesis and is a promising biomarker for OSCC prediction. Studies suggest further validation in large distinct cohorts to facilitate translation to clinics.

AB - Introduction The relevance of DNA methylation of O6-methylguanine-DNA methyltransferase (MGMT) in relation to several cancers and other disorders has been extensively explored in several cancer types. Aims To ascertain the significance of DNA methylation of MGMT promoter in oral squamous cell carcinoma (OSCC), we undertook a study to a) analyse the methylation patterns of MGMT gene promoter in afflicted and normal population of coastal Karnataka, b) determine the expression status of MGMT in oral cancer cell lines (CAL-27 and SCC-4) and its relationship to DNA methylation and c) performed a meta-analysis of the published data. Methods Bisulfite sequencing of MGMT promoter region was performed on non-malignant/malignant oral samples, and oral cancer cell lines, followed by gene expression studies. Further, using a systematic search, 1024 publications were retrieved from PubMed, Scopus, Google Scholar and Web of Science and 23 relevant articles were reviewed. Results Significant association of MGMT promoter methylation with OSCC (p < 0.0001) was observed in the case-control study. The studies chosen for meta-analysis showed predictive significance of MGMT gene promoter. Overall, we obtained a statistically significant (p < 0.0001) association for both sensitivity and specificity of MGMT DNA promoter methylation in oral cancer cases without publication bias. Gene expression was significantly elevated in both oral cancer cell lines (p < 0.03) after treatment with a demethylating agent (5-Aza-2′-deoxycytidine). Conclusion DNA promoter hypermethylation and gene expression of MGMT may associate with recursive mutagenesis and is a promising biomarker for OSCC prediction. Studies suggest further validation in large distinct cohorts to facilitate translation to clinics.

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U2 - 10.1016/j.archoralbio.2017.04.006

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