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

BMC Cancer

Research Article

Yoshiyuki Mori¹  Takahiro Abe²  Tsuyoshi Takato²  Hideto Saijo²  Kazuto Hoshi²  Masanobu Abe³  Toshikazu Ushijima⁴  Satoshi Yamashita⁴ 

[1] Department of Dentistry, Oral & Maxillofacial Surgery, Jichi Medical University, Tochigi, Japan;Department of Oral & Maxillofacial Surgery, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan;Department of Oral & Maxillofacial Surgery, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan;Division for Health Service Promotion, University of Tokyo, Tokyo, Japan;Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan;

关键词: Methylation;    Promoter methylation;    Gene silencing;    Oral squamous cell carcinoma;    Oral leukoplakia;   

DOI  :  10.1186/s12885-016-2371-5

 received in 2015-11-25, accepted in 2016-05-19,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundEarly 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.MethodsTo 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.ResultsA 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).ConclusionsOLs at high risk for malignant transformation were associated with aberrant promoter methylation of multiple genes.

【 授权许可】

CC BY   
© The Author(s). 2016