DNA Methylation Changes in Clinical Stages of Oral Cancer Progression and Correlation with DOC2B Promoter Hypermethylation

Radhakrishnan, Raghu and Raghavendra, Upadhya and Aithal, Abhijit and Prasada, Shama and Bhat, Samatha and Jayaprakash, Chinchu and Ray, Satadru and Kamath, Asha and Satyamoorthy, K (2013) DNA Methylation Changes in Clinical Stages of Oral Cancer Progression and Correlation with DOC2B Promoter Hypermethylation. Molecular Cancer Biology. pp. 1-13. ISSN 2168-0922

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Abstract

The well-established correlation between global DNA hypomethylation and genomic instability offers one of the mechanistic explanations on how hypomethylation may contribute to carcinogenesis. In our study, levels of 5-methyl -2’-deoxycytidine in oral cancer tissues and microdissected DNA analysed by reverse phase – high performance liquid chromatograp hy (RP-HPLC) revealed a generalized decrease in all oral cancer samples (1.63 ± 0.16) compared to its matched normal counte rpart (3.67 ± 0.17; P 0.001). Validation of global DNA methylation as ana lysed by immunohistochemistry (IHC) in successive stages of oral cancer progression in tissue sections using antibody to 5- methyl cytosine revealed reduced immunostaining in dysplasia and oral squamous cell carcinomas (OSCC) compared to normal oral mucosal epithelium. Methylation sensitive arbitrarily primed polymerase chain reaction (MS-AP-PCR) identified se veral non-canonical CpG rich fragments including promoter region of DOC2B ( Double C2 like Domain B) gene spanning -376bp to + 36bp. This was found to be methylated in oral cancer tissues, confirmed by methylation sensitive dimethyl sulfoxide polymerase chain reaction (MS-DMSO-PCR) and validated by bisu lfite genome sequencing (BGS). DOC2B promoter and other differentially methylated sequences identified in our stud y may serve as potential diagnostic markers to delineate human oral cancer and suggests oral cancer patho genesis to altered epigenetic mechanisms.

Item Type: Article
Uncontrolled Keywords: DNA methylation; oral cancer; Global hypomethylation; DOC2B promoter, hypermethylation, RP-HPLC, Ms-AP-PCR
Subjects: Dentistry > MCODS Manipal > Oral Pathology and Microbiology
Departments at MU > Statistics
Life Sciences > MLSC Manipal
Medicine > KMC Manipal > Surgical Oncology
Depositing User: KMC Manipal
Date Deposited: 15 Jan 2014 07:24
Last Modified: 15 Jan 2014 07:24
URI: http://eprints.manipal.edu/id/eprint/138353

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