Identification of genes specifically methylated in Epstein–Barr virus‐associated gastric carcinomas

We studied the comprehensive DNA methylation status in the naturally derived gastric adenocarcinoma cell line SNU‐719, which was infected with the Epstein–Barr virus (EBV) by methylated CpG island recovery on chip assay. To identify genes specifically methylated in EBV‐associated gastric carcinomas...

Full description

Saved in:
Bibliographic Details
Published in:Cancer science 2013-10, Vol.104 (10), p.1309-1314
Main Authors: Okada, Toshiyuki, Nakamura, Munetaka, Nishikawa, Jun, Sakai, Kouhei, Zhang, Yibo, Saito, Mari, Morishige, Akihiro, Oga, Atsunori, Sasaki, Kosuke, Suehiro, Yutaka, Hinoda, Yuji, Sakaida, Isao
Format: Article
Language:English
Subjects:
Aged
Azacitidine - analogs & derivatives
Azacitidine - pharmacology
Carcinoma - genetics
Carcinoma - virology
Cell Line, Tumor
DNA Methylation
DNA, Neoplasm - chemistry
DNA, Neoplasm - genetics
DNA-Binding Proteins - genetics
Epstein-Barr virus
Epstein-Barr Virus Infections - genetics
Female
Gene Expression Regulation, Neoplastic - drug effects
Genes, Tumor Suppressor
Homeodomain Proteins - genetics
Humans
Hydroxamic Acids - pharmacology
Male
Microfilament Proteins - genetics
Middle Aged
Neoplasm Proteins - genetics
Nerve Tissue Proteins - genetics
Nuclear Proteins - genetics
Oncogene Proteins - genetics
Original
Promoter Regions, Genetic
Protein-Serine-Threonine Kinases - genetics
Real-Time Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Neoplasm - genetics
Stomach Neoplasms - genetics
Stomach Neoplasms - virology
Transcription Factors - genetics
Tumor Protein p73
Tumor Suppressor Proteins - genetics
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We studied the comprehensive DNA methylation status in the naturally derived gastric adenocarcinoma cell line SNU‐719, which was infected with the Epstein–Barr virus (EBV) by methylated CpG island recovery on chip assay. To identify genes specifically methylated in EBV‐associated gastric carcinomas (EBVaGC), we focused on seven genes, TP73, BLU, FSD1, BCL7A, MARK1, SCRN1, and NKX3.1, based on the results of methylated CpG island recovery on chip assay. We confirmed DNA methylation of the genes by methylation‐specific PCR and bisulfite sequencing in SNU‐719. The expression of the genes, except for BCL7A, was upregulated by a combination of 5‐Aza‐2′‐deoxycytidine and trichostatin A treatment in SNU‐719. After the treatment, unmethylated DNA became detectable in all seven genes by methylation‐specific PCR. We verified DNA methylation of the genes in 75 primary gastric cancer tissues from 25 patients with EBVaGC and 50 EBV‐negative patients who were controls. The methylation frequencies of TP73, BLU, FSD1, BCL7A, MARK1, SCRN1, and NKX3.1 were significantly higher in EBVaGC than in EBV‐negative gastric carcinoma. We identified seven genes with promoter regions that were specifically methylated in EBVaGC. Inactivation of these genes may suppress their function as tumor suppressor genes or tumor‐associated antigens and help to develop and maintain EBVaGC.
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.12228