Hypermethylation of MGMT and DAPK gene promoters is associated with tumorigenesis and metastasis in oral squamous cell carcinoma

Background/purpose: Oral squamous cell carcinoma (OSCC) is the fourth major cause of mortality among males in Asia. The tumorigenesis of OSCC is a multi-step process characterized by sequential morphological changes. The extent of lymph node metastasis is a major determinant in the prognosis of canc...

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Main Authors: Yong-Kie Wong, Li-Tsu Lee, Chung-Ji Liu
Format: Article
Language:English
Published: Elsevier 2011-09-01
Series:Journal of Dental Sciences
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1991790211000560
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author Yong-Kie Wong
Li-Tsu Lee
Chung-Ji Liu
author_facet Yong-Kie Wong
Li-Tsu Lee
Chung-Ji Liu
author_sort Yong-Kie Wong
collection DOAJ
description Background/purpose: Oral squamous cell carcinoma (OSCC) is the fourth major cause of mortality among males in Asia. The tumorigenesis of OSCC is a multi-step process characterized by sequential morphological changes. The extent of lymph node metastasis is a major determinant in the prognosis of cancer. Hypermethylation is an important pathway for repression of gene transcription in cancer cells and a promising marker for cancer detection. It is also found in early metastatic cancer patients. Materials and methods: Sixty-four histologically confirmed OSCC tissues and corresponding nontumorous tissues were enrolled in this study. DNA was extracted. The promoter methylation status of the p16, death-associated protein kinase (DAPK), MGMT, and glutathione S-transferase genes in OSCC tissues was evaluated by a methylation-specific polymerase chain reaction analysis. Results: Frequencies of promoter hypermethylation of p16, DAPK, and MGMT in OSCC tissue were 67.2%, 45.3%, and 31.3%, respectively. No methylation was found in normal oral mucosa. Methylation rates of MGMT (50%) and DAPK (55.6%) in metastasized OSCC were higher than those of MGMT (23.9%) and DAPK (41.3%) in nonmetastasized OSCC. No glutathione S-transferase P methylation was found in any tissue samples. Conclusions: Our study supports the hypothesis that hypermethylation of p16 gene promoters may indicate a high risk of oral cancer, and hypermethylation of the MGMT and DAPK genes may be a major indicator of early OSCC metastasis.
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spelling doaj.art-3d631ed614ba496cb04cb1dd52be85c92022-12-22T01:27:12ZengElsevierJournal of Dental Sciences1991-79022011-09-016315816410.1016/j.jds.2011.05.006Hypermethylation of MGMT and DAPK gene promoters is associated with tumorigenesis and metastasis in oral squamous cell carcinomaYong-Kie Wong0Li-Tsu Lee1Chung-Ji Liu2Department of Oral and Maxillofacial Surgery, Taichung Veterans General Hospital, Taichung, TaiwanDepartment of Oral and Maxillofacial Surgery, Taichung Veterans General Hospital, Taichung, TaiwanDental School of National Yang Ming University, Taipei, TaiwanBackground/purpose: Oral squamous cell carcinoma (OSCC) is the fourth major cause of mortality among males in Asia. The tumorigenesis of OSCC is a multi-step process characterized by sequential morphological changes. The extent of lymph node metastasis is a major determinant in the prognosis of cancer. Hypermethylation is an important pathway for repression of gene transcription in cancer cells and a promising marker for cancer detection. It is also found in early metastatic cancer patients. Materials and methods: Sixty-four histologically confirmed OSCC tissues and corresponding nontumorous tissues were enrolled in this study. DNA was extracted. The promoter methylation status of the p16, death-associated protein kinase (DAPK), MGMT, and glutathione S-transferase genes in OSCC tissues was evaluated by a methylation-specific polymerase chain reaction analysis. Results: Frequencies of promoter hypermethylation of p16, DAPK, and MGMT in OSCC tissue were 67.2%, 45.3%, and 31.3%, respectively. No methylation was found in normal oral mucosa. Methylation rates of MGMT (50%) and DAPK (55.6%) in metastasized OSCC were higher than those of MGMT (23.9%) and DAPK (41.3%) in nonmetastasized OSCC. No glutathione S-transferase P methylation was found in any tissue samples. Conclusions: Our study supports the hypothesis that hypermethylation of p16 gene promoters may indicate a high risk of oral cancer, and hypermethylation of the MGMT and DAPK genes may be a major indicator of early OSCC metastasis.http://www.sciencedirect.com/science/article/pii/S1991790211000560hypermethylationmetastasismouth neoplasmMS-PCRp16/MGMT/GSTP1/DAPK
spellingShingle Yong-Kie Wong
Li-Tsu Lee
Chung-Ji Liu
Hypermethylation of MGMT and DAPK gene promoters is associated with tumorigenesis and metastasis in oral squamous cell carcinoma
Journal of Dental Sciences
hypermethylation
metastasis
mouth neoplasm
MS-PCR
p16/MGMT/GSTP1/DAPK
title Hypermethylation of MGMT and DAPK gene promoters is associated with tumorigenesis and metastasis in oral squamous cell carcinoma
title_full Hypermethylation of MGMT and DAPK gene promoters is associated with tumorigenesis and metastasis in oral squamous cell carcinoma
title_fullStr Hypermethylation of MGMT and DAPK gene promoters is associated with tumorigenesis and metastasis in oral squamous cell carcinoma
title_full_unstemmed Hypermethylation of MGMT and DAPK gene promoters is associated with tumorigenesis and metastasis in oral squamous cell carcinoma
title_short Hypermethylation of MGMT and DAPK gene promoters is associated with tumorigenesis and metastasis in oral squamous cell carcinoma
title_sort hypermethylation of mgmt and dapk gene promoters is associated with tumorigenesis and metastasis in oral squamous cell carcinoma
topic hypermethylation
metastasis
mouth neoplasm
MS-PCR
p16/MGMT/GSTP1/DAPK
url http://www.sciencedirect.com/science/article/pii/S1991790211000560
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AT litsulee hypermethylationofmgmtanddapkgenepromotersisassociatedwithtumorigenesisandmetastasisinoralsquamouscellcarcinoma
AT chungjiliu hypermethylationofmgmtanddapkgenepromotersisassociatedwithtumorigenesisandmetastasisinoralsquamouscellcarcinoma