DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis

Abstract

Transcriptional silencing by CpG island hypermethylation is a potential mechanism for the inactivation of tumor-related genes. Virtually, all types of human cancers show CpG island hypermethylation, and gastric carcinoma (GC) is one of the tumors with a high frequency of aberrant CpG island hypermethylation. In this study, we prescreened DNA methylation of 170 CpG island loci in a training set of 8 paired GC and GC-associated non-neoplastic mucosae (GCN) using MethyLight technology and selected 27 DNA methylation markers showing higher methylation frequency or level in GC than in GCN. These markers were then analyzed in a tester set of 25 paired GC and GCN and 27 chronic gastritis (CG) from non-cancer patients to generate their DNA methylation profiles. We identified 17 novel methylation markers in GC, including SFRP4, SEZ6L, TWIST1, BCL2, KL, TERT, SCGB3A1, IGF2, GRIN2B, SFRP5, DLEC1, HOXA1, CYP1B1, SMAD9, MT1G, NR3C1, and HOXA10. Of the 27 selected CpG island loci, 23 were methylated in GC, GCN, and CG and the remainder four loci (DLEC1, CHFR, CYP1B1, and NR3C1) were only methylated in GC. We found that the number of methylated loci was significantly higher in GC than in GCN or CG and that Helicobacter pylori infection was strongly associated with aberrant CpG island hypermethylation in CG. Hypermethylation was more prevalent in Epstein-Barr virus (EBV)-positive GC than in EBV-negative GC and in diffuse-type GC than in intestinal-type GC. Through our large-scale screening of 170 CpG island loci, we found 17 new DNA methylation markers of GC, which may serve as useful markers that may identify a distinct subset of GC.

High-definition CpG methylation of novel genes in gastric carcinogenesis identified by next-generation sequencing

“…35 The gene with the highest correlation between methylation and expression was CHFR (checkpoint with forkhead and ring finger domains gene), an E3 ubiquitin ligase critically involved in a mitosis checkpoint that prevents errors during chromosome segregation. In a previous study, methylation of CHFR was observed in 39% of the gastric cancers and loss of CHFR expression was associated with sensitivity of gastric cancer cells to microtubule NGS methylation analysis in gastric carcinogenesis inhibitors, 34 although this association has been controversial.…”

Screening of Differential Promoter Hypermethylated Genes in Primary Oral Squamous Cell Carcinoma

“…DNA methylation is one of the epigenetic phenomena that occur at the molecular level involving regulation of cell of development and differentiation, aging, and diseases (Shaw, 2006;Supic, et al, 2009). Notably, most of the gene inactivation mechanism involved in cancer progression is the promoter hypermethylation of CpG islands (Kang et al, 2007;Noushmehret al, 2010). This process is now widely recognized as either a causative or correlative event in carcinogenesis (Herman and Baylin, 2003;Jones, 2012).…”

Secreted frizzled related proteins: Implications in cancers

“…The incidence of gastric carcinoma (GC) is highest in Eastern Asia, Eastern Europe, and South America while the lowest rates are in Africa and North America [140,141]. During cancer development, aberrant CpG island hypermethylation is found to occur frequently in the stomach [142].…”