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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

High-risk oral leukoplakia is associated with aberrant promoter methylation of multiple genes

Authors: Masanobu Abe, Satoshi Yamashita, Yoshiyuki Mori, Takahiro Abe, Hideto Saijo, Kazuto Hoshi, Toshikazu Ushijima, Tsuyoshi Takato

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Early detection of oral squamous cell carcinomas (OSCCs) is urgently needed to improve the prognosis and quality of life (QOL) of patients. Oral leukoplakias (OLs), known as the most common premalignant lesions in the oral cavity, often precede OSCCs. Especially, OLs with dysplasia are known to have a high risk of malignant transformation. Here, we searched for the promoter methylation characteristic of high-risk OLs.

Methods

To identify methylation-silenced genes, a combined analysis of methylated DNA immunoprecipitation (MeDIP) − CpG island (CGI) microarray analysis and expression microarray analysis after treatment with a demethylating agent was performed in two OSCC cell lines (Ca9–22 and HSC-2). The methylation statuses of each gene were examined by methylation-specific PCR.

Results

A total of 52 genes were identified as candidates for methylation-silenced genes in Ca9-22 or HSC-2. The promoter regions of 13 genes among the 15 genes randomly selected for further analysis were confirmed to be methylated in one or more of five cell lines. In OSCC tissues (n = 26), 8 of the 13 genes, TSPYL5, EGFLAM, CLDN11, NKX2-3, RBP4, CMTM3, TRPC4, and MAP6, were methylated. In OL tissues (n = 24), seven of the eight genes, except for EGFLAM, were found to be methylated in their promoter regions. There were significantly greater numbers of methylated genes in OLs with dysplasia than in those without dysplasia (p < 0.0001).

Conclusions

OLs at high risk for malignant transformation were associated with aberrant promoter methylation of multiple genes.
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Metadata
Title
High-risk oral leukoplakia is associated with aberrant promoter methylation of multiple genes
Authors
Masanobu Abe
Satoshi Yamashita
Yoshiyuki Mori
Takahiro Abe
Hideto Saijo
Kazuto Hoshi
Toshikazu Ushijima
Tsuyoshi Takato
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2371-5

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