Analysis of DNA methylation patterns associated with the gastric cancer genome

Abstract

The objective of the current study was to investigate the characteristics of DNA methylation patterns associated with the gastric cancer genome and to identify clinically useful diagnostic markers and therapeutic targets for gastric cancer. The Infinium 450K methylation microarray was used to compare differential DNA methylation sites of gastric cancer tissue with that of normal gastric tissue. The results of the DNA microarray analysis were confirmed by pyrosequencing. Functional analysis of the differential genes was performed using the GO software. The effect of candidate site methylation on gene expression was monitored using quantitative polymerase chain reaction analysis. Of the 2,645 differential methylation sites identified in gastric cancer tissues, 2,016 were hypermethylated sites, 629 were hypomethylated sites, 826 were located in promoter regions and 1,024 were located within genes. These differential sites were associated with 1,352 genes. In total, five sites were selected and pyrosequencing verified the results of the microarray analysis in five of the sites. Change in gastric cancer DNA methylation pattern was a common occurrence. Differential methylation sites appeared more often in non-promoter regions. The associated genes were involved in multiple signaling pathways, and hypermethylated and hypomethylated sites were involved in roughly the same signaling pathways. Methylation of the genome promoted gene expression. TRIM15, ITGAM, MSX2 and FAM38A may be candidate genes for diagnosing gastric cancer.

Development and Validation of a Prognostic Nomogram for Gastric Cancer Based on DNA Methylation-Driven Differentially Expressed Genes

“…DNA methylation (DNAm) is an important epigenetic event that can influence pretranscriptional gene silencing, genetic imprinting, X-chromosome inactivation (XCI), genome stability, and cell fate determination [9]. De novo methyltransferases, namely, DNMT3A and DNMT3B [10,11], play a vital role in tumorigenesis mainly by methylating CpG dinucleotides [12]. Aberrant DNAm in the promoter regions is generally believed to be a hallmark of tumors, which often leads to the transcriptional silencing of tumor suppressor genes (TSGs) and the abnormal activation of oncogenes in tumor cells [13].…”

Genome‐wide profiling of normal gastric mucosa identifies Helicobacter pylori‐ and cancer‐associated DNA methylome changes

“…H. pylori and the inflammatory process it triggers may promote GC development by inducing deregulation of the DNA methylome . A number of studies have conducted DNA methylation analysis in GC tumours and their adjacent tissues using candidate gene or genome‐wide approaches; however, these studies were limited to cancer tissue, and the effects of H. pylori were not considered. Three studies have identified methylation signatures in normal gastric mucosa in response to H. pylori infection, but these involved only several genes or partial DNA methylome coverage or did not include GC patients .…”

Epigenetic clustering of gastric carcinomas based on DNA methylation profiles at the precancerous stage: its correlation with tumor aggressiveness and patient outcome

“…Although studies of gastric carcinomas ( 27 , 28 ) employing the single-CpG resolution Infinium array ( 29 ) have recently been published, they did not focus on DNA methylation in the non-cancerous mucosa. In this study, in order to clarify the significance of DNA methylation alterations at the precancerous stage of gastric carcinogenesis, we subjected 109 samples of non-cancerous mucosa (N) obtained from 109 patients with primary gastric carcinomas, and 105 samples of the corresponding tumorous tissues (T), to the Infinium assay.…”