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Genome-wide DNA methylation profile identified a unique set of differentially methylated immune genes in oral squamous cell carcinoma patients in India

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Title Genome-wide DNA methylation profile identified a unique set of differentially methylated immune genes in oral squamous cell carcinoma patients in India
 
Creator Basu, Baidehi
Chakraborty, Joyeeta
Chandra, Aditi
Katarkar, Atul
Baldevbhai, Jadav Ritesh Kumar
Dhar Chowdhury, Debjit
Roy, Jay GopaL
Chaudhuri, Keya
Chatterjee, Raghunath
 
Subject Molecular & Human Genetics
 
Description Background: Oral squamous cell carcinoma (OSCC) is one of the common malignancies in Southeast Asia.
Epigenetic changes, mainly the altered DNA methylation, have been implicated in many cancers. Considering the
varied environmental and genotoxic exposures among the Indian population, we conducted a genome-wide DNA
methylation study on paired tumor and adjacent normal tissues of ten well-differentiated OSCC patients and
validated in an additional 53 well-differentiated OSCC and adjacent normal samples.
Results: Genome-wide DNA methylation analysis identified several novel differentially methylated regions
associated with OSCC. Hypermethylation is primarily enriched in the CpG-rich regions, while hypomethylation is
mainly in the open sea. Distinct epigenetic drifts for hypo- and hypermethylation across CpG islands suggested
independent mechanisms of hypo- and hypermethylation in OSCC development. Aberrant DNA methylation in the
promoter regions are concomitant with gene expression. Hypomethylation of immune genes reflect the
lymphocyte infiltration into the tumor microenvironment. Comparison of methylome data with 312 TCGA HNSCC
samples identified a unique set of hypomethylated promoters among the OSCC patients in India. Pathway analysis
of unique hypomethylated promoters indicated that the OSCC patients in India induce an anti-tumor T cell
response, with mobilization of T lymphocytes in the neoplastic environment. Survival analysis of these
epigenetically regulated immune genes suggested their prominent role in OSCC progression.
Conclusions: Our study identified a unique set of hypomethylated regions, enriched in the promoters of immune
response genes, and indicated the presence of a strong immune component in the tumor microenvironment.
These methylation changes may serve as potential molecular markers to define risk and to monitor the prognosis
of OSCC patients in India.
 
Date 2017-02-03
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2607/1/Clinical_Epigenetics_(2017).pdf
Basu, Baidehi and Chakraborty, Joyeeta and Chandra, Aditi and Katarkar, Atul and Baldevbhai, Jadav Ritesh Kumar and Dhar Chowdhury, Debjit and Roy, Jay GopaL and Chaudhuri, Keya and Chatterjee, Raghunath (2017) Genome-wide DNA methylation profile identified a unique set of differentially methylated immune genes in oral squamous cell carcinoma patients in India. Clinical Epigenetics, 9 (13). 01p. -15p..
 
Relation http://dx.doi.org/10.1186/s13148-017-0314-x
http://www.eprints.iicb.res.in/2607/