Gene methylation in gastric cancer

Abstract

Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field.

Global methylation and promoter-specific methylation of the P16, SOCS-1, E-cadherin, P73 and SHP-1 genes and their expression in patients with multiple myeloma during active disease and remission

“…cells (37,38). It has been identified that there is an association between hypermethylation of SOCS-1 and the pathogenesis of different tumors, including chronic myeloid leukemia, human melanoma and gastric cancer (39)(40)(41) (43) failed to detect a correlation between P16 methylation and prognostic factors. P16 hypermethylation has been associated with progression of the disease, as the frequency of this phenomena increases as the disease progresses through its different stages of evolution, beginning at 0% at the preclinical phase or monoclonal gammopathy of undetermined significance, at 0% for the asymptomatic phase, and to 41.8% for symptomatic MM and 80% for plasma cell leukemia (3,4,20,21).…”

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

“…Homeostasis of the gastrointestinal epithelium is 87 [47,[69][70][71][72][73][74][75]232] Fzd-3 [78] CTNNB1 [9,[88][89][90][91][92][93]96,97] LRP6 [228] TCF7L2 [98][99][100] PPN [79] CDH17 [80] EZH2 [81] HMGA1, HMGA2 [210,211] YY1 [86] TC1 (C8orf4) [201,202] miR-17-92 [161] mir-10a [168] has-miR-335 [166] hsa-miR-375 [163] Downregulation or function inhibition in gastric cancer Downregulation by hypermethylation Inactivation by miRNAs APC [145,146] APC [175] sFRP1, sFRP2, sFRP4, sFRP5 [78,96,149] AXIN2 [159] WIF-1 [144,149] EZF1 [78] Dkk-1, Dkk-2, Dkk-3 [59,144,148,…”

“…Indeed, APC is one of the genes commonly hypermethylated in gastric cancer [145,146] . Moreover, hypermethylation of APC promoter contributing to moderate activation of Wnt signaling was associated to the development and progression of gastric adenomas, which are considered as premalignant lesions of gastric adenocarcinoma [145] .…”

Epstein-Barr Virus and DNA Methylation in Gastric Cancer

“…DNA methylation occurs by the addition of a methyl (CH 3 ) group to the fifth carbon of cytosine residues in CpG islands (2,6). CpG islands are located in the promoter regions of about half of all of the genes in the genome and are regions rich with guanine and cytosine.…”

“…Physiologically, DNA methylation is seen in events such as X chromosome inactivation, differentiation in the stage of embryogenesis, and genomic imprinting (6). DNA methylation is catalyzed by the enzymes called DNA methyltransferase (DNMT) (6). While the continuity of DNA methylation occurs with the enzyme DNMT1, DNMT3A and DNMT3B enzymes serve in de novo DNA methylation (7).…”