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

Raghu Radhakrishnan, Aithal Abhijit, Shama P Kabekkodu, Samatha Bhat, Chinju jayaprakash, Ray S, Prasad KC, Kamath A, Lene R, Satyamoorthy Kapaettu

Research output: Contribution to journalArticle

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.
Original languageEnglish
JournalMolecular Cancer Biology
Publication statusPublished - 2013

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Mouth Neoplasms
DNA Methylation
5-methyldeoxycytidine
Methylation
Polymerase Chain Reaction
Genomic Instability
Cytosine
DNA
Dimethyl Sulfoxide
Genetic Promoter Regions
Epigenomics
Squamous Cell Carcinoma
Carcinogenesis
Epithelium
Immunohistochemistry
Genome
Antibodies
Genes

Cite this

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title = "DNA Methylation Changes in Clinical Stages of Oral Cancer Progression and Correlation with DOC2B Promoter Hypermethylation",
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.",
author = "Raghu Radhakrishnan and Aithal Abhijit and Kabekkodu, {Shama P} and Samatha Bhat and Chinju jayaprakash and Ray S and Prasad KC and Kamath A and Lene R and Satyamoorthy Kapaettu",
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DNA Methylation Changes in Clinical Stages of Oral Cancer Progression and Correlation with DOC2B Promoter Hypermethylation. / Radhakrishnan, Raghu; Abhijit, Aithal; Kabekkodu, Shama P; Bhat, Samatha; jayaprakash, Chinju; S, Ray; KC, Prasad ; A, Kamath; R, Lene ; Kapaettu, Satyamoorthy.

In: Molecular Cancer Biology, 2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - DNA Methylation Changes in Clinical Stages of Oral Cancer Progression and Correlation with DOC2B Promoter Hypermethylation

AU - Radhakrishnan, Raghu

AU - Abhijit, Aithal

AU - Kabekkodu, Shama P

AU - Bhat, Samatha

AU - jayaprakash, Chinju

AU - S, Ray

AU - KC, Prasad

AU - A, Kamath

AU - R, Lene

AU - Kapaettu, Satyamoorthy

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

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