DNA Methylation and Genetic Aberrations in Gastric Cancer.

Background: Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. GC is a pathologically and molecularly heterogeneous disease. DNA hypermethylation in promoter CpG islands causes silencing of tumor-suppressor genes and thus contributes to gastric carcinogenesis.

Epstein-Barr virus-positive gastric cancer involves enhancer activation through activating transcription factor 3.

Epstein-Barr virus (EBV) is associated with particular forms of gastric cancer (GC). We previously showed that EBV infection into gastric epithelial cells induced aberrant DNA hypermethylation in promoter regions and silencing of tumor suppressor genes. We here undertook integrated analyses of transcriptome and epigenome alteration during EBV infection in gastric cells, to investigate activation of enhancer regions and related transcription factors (TFs) that could contribute to tumorigenesis.

DNMT3A overexpression is associated with aggressive behavior and enteroblastic differentiation of gastric adenocarcinoma.

Gastric adenocarcinoma (GA) with enteroblastic differentiation is a subset of gastric cancer with poor prognosis. RNA-Seq data of The Cancer Genome Atlas of GA (TCGA-STAD) revealed a positive correlation between SALL4, a representative enteroblastic marker, and DNMT3A expression. Here, we conducted immunohistochemical analysis of GA to clarify the clinicopathological significance of DNMT3A expression and its correlation with enteroblastic differentiation.

Histone modification alteration coordinated with acquisition of promoter DNA methylation during Epstein-Barr virus infection.

Aberrant DNA hypermethylation is a major epigenetic mechanism to inactivate tumor suppressor genes in cancer. Epstein-Barr virus positive gastric cancer is the most frequently hypermethylated tumor among human malignancies. Herein, we performed comprehensive analysis of epigenomic alteration during EBV infection, by Infinium HumanMethylation 450K BeadChip for DNA methylation and ChIP-sequencing for histone modification alteration during EBV infection into gastric cancer cell line MKN7.

Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus.

Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) gastric cancer presents an extremely high-methylation epigenotype and this aberrant DNA methylation causes silencing of multiple tumour suppressor genes. However, the mechanisms that drive EBV infection-mediated tumorigenesis, including other epigenomic alteration, remain unclear.

Epstein-Barr virus infection induces genome-wide de novo DNA methylation in non-neoplastic gastric epithelial cells.

Epstein-Barr virus (EBV)-positive gastric cancer (GC) shows a higher DNA methylation epigenotype. EBV infection can causally induce genome-wide aberrant DNA methylation, as previously demonstrated by in vitro infection experiments in the low-methylation GC cell line MKN7. However, whether EBV exerts DNA methylation remodelling properties in non-neoplastic epithelial cells remains unclear.

TET2 functions as a resistance factor against DNA methylation acquisition during Epstein-Barr virus infection.

Extensive DNA methylation is observed in gastric cancer with Epstein-Barr virus (EBV) infection, and EBV infection is the cause to induce this extensive hypermethylaton phenotype in gastric epithelial cells. However, some 5' regions of genes do not undergo de novo methylation, despite the induction of methylation in surrounding regions, suggesting the existence of a resistance factor against DNA methylation acquisition. We conducted an RNA-seq analysis of gastric epithelial cells with and without EBV infection and found that TET family genes, especially TET2, were repressed by EBV infection at both mRNA and protein levels.

Host SHP1 phosphatase antagonizes Helicobacter pylori CagA and can be downregulated by Epstein-Barr virus.

Most if not all gastric cancers are associated with chronic infection of the stomach mucosa with Helicobacter pylori cagA-positive strains(1-4). Approximately 10% of gastric cancers also harbour Epstein-Barr virus (EBV) in the cancer cells(5,6). Following delivery into gastric epithelial cells via type IV secretion(7,8), the cagA-encoded CagA protein undergoes tyrosine phosphorylation on the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs initially by Src family kinases (SFKs) and then by c-Abl(9,10).

DNA methylation accumulation and its predetermination of future cancer phenotypes.

Aberant DNA methylation is a common epigenomic alteration in carcinogenesis. Comprehensive analyses of DNA methylation have stratified gastrointestinal cancer into several subgroups according to specific DNA methylation accumulation. In gastric cancer, Helicobacter pylori infection is a cause of methylation accumulation in apparently normal mucosa.

DNA methylation in gastric cancer, related to Helicobacter pylori and Epstein-Barr virus.

Gastric cancer is a leading cause of cancer death worldwide, and significant effort has been focused on clarifying the pathology of gastric cancer. In particular, the development of genome-wide analysis tools has enabled the detection of genetic and epigenetic alterations in gastric cancer; for example, aberrant DNA methylation in gene promoter regions is thought to play a crucial role in gastric carcinogenesis. The etiological viewpoint is also essential for the study of gastric cancers, and two distinct pathogens, Helicobacter pylori (H.