Gene methylation in gastric cancer

Clin Chim Acta. 2013 Sep 23;424:53-65. doi: 10.1016/j.cca.2013.05.002. Epub 2013 May 10.


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.

Keywords: 5-hmC; 5-hydroxymethylcytosine; 5-mC; 5-methylcytosine; ADAM metallopeptidase domain 23; ADAM metallopeptidase with thrombospondin type 1 motif, 9; ADAM23; ADAMTS9; AML; APC; ARID1A; AT motif-binding factor 1; AT rich interactive domain 1A (SWI-like); ATBF1; Acute myelocytic leukemia; Adenomatosis polyposis coli; B-cell translocation gene 4; BCL2/adenovirus E1B 19kDa interacting protein 3; BMP-2; BNIP3; BS; BTG4; Biomarkers; Bisulfite sequencing; Bone morphogenetic protein 2; C-MET; CACNA1G; CACNA2D3; CD44; CD44 molecule (Indian blood group); CDH1; CDK4; CDK6; CDKN1C; CDKN2A; CDX2; CGI; CHD5; CHFR; CKLF-like MARVEL transmembrane domain containing 3; CMTM3; CNS; CRBP1; Cadherin 1 or E-cadherin; Calcium channel, voltage-dependent, T type, alpha 1G subunit; Calcium channel, voltage-dependent, alpha 2/delta subunit 3; Caudal type homeobox 2; Central nervous system; Checkpoint with forkhead and ring finger domains, E3 ubiquitin protein ligase; Chromodomain helicase DNA binding protein 5; Chromosome 2 open reading frame 40; Clinical outcomes; CpG islands; Cyclin-dependent kinase 4; Cyclin-dependent kinase 6; Cyclin-dependent kinase inhibitor 1A; Cyclin-dependent kinase inhibitor 1B; Cyclin-dependent kinase inhibitor 1C; Cyclin-dependent kinase inhibitor 2A; Cyclin-dependent kinase inhibitor 2B; DAB2 interacting protein; DACT1; DAPK; DNA; DNA methylatransferases; DNA mismatch repair; DNMT; Dapper, antagonist of beta-catenin, homolog 1 (Xenopus laevis); Death-associated protein kinase; Deoxyribose Nucleic Acid; Dickkopf 3 homolog (Xenopus laevis); Dkk-3; EBV; ECRG4; EDNRB; EGCG; ERBB4; Endothelin receptor type B; Epigallocatechin gallate; Epigenetics; Epstein–Barr Virus; FDA; FLNc; Filamin C; Food and Drug Administration; GC; GDNF; GI endoscopy; GPX3; GRIK2; GSTP1; Gastric cancer; Gene methylation; Glutamate receptor, ionotropic, kainate 2; Glutathione S-transferase pi 1; Glutathione peroxidase 3 (plasma); H. pylori; HACE1; HAI-2/SPINT2; HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1; HGFA; HLTF; HOXA1; HOXA10; HRAS-like suppressor; HRASLS; Helicase-like transcription factor; Helicobacter pylori; Homeobox A1; Homeobox A10; Homeobox D10; HoxD10; IGF-1; IGF-1R; IGFBP3; IL-1β; ITGA4; Insulin-like growth factor 1 (somatomedin C); Insulin-like growth factor I receptor; Insulin-like growth factor binding protein 3; Integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor); Interleukin 1, beta; KL; KRAS; Klotho; LL3; LMP2A; LOX; LRP1B; Low density lipoprotein receptor-related protein 1B; Lysyl oxidase; MAPK; MBPs; MDS; MGMT; MINT25; MLF1; MLL; MMR; MSI; MSP; Matrix metallopeptidase 24 (membrane-inserted); Met proto-oncogene (hepatocyte growth factor receptor); Methyl-CpG binding proteins; Methylation-specific PCR; Microsatellite instability; Myeloid leukemia factor 1; Myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); Myeloid/lymphoid or mixed-lineage leukemia 3; NDRG family member 2; NDRG2; NPR1; NR3C1; Natriuretic peptide receptor A/guanylate cyclase A; Notch 1; Nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor); O-6-methylguanine-DNA methyltransferase; PCDH10; PCDH17; PI3K/Akt; PIK3CA; PR domain containing 5; PRDM5; PTCH1; Patched 1; Phosphatidylethanolamine binding protein 1; Protein tyrosine phosphatase, non-receptor type 6; Protocadherin 10; Protocadherin 17; Q-MSP; Quantitative methylation-specific PCR; RAR-related orphan receptor A; RARRES1; RARß; RAS/RAF/MEK/ERK; RASSF1A; RASSF2; RBP1; RKIP; RORA; ROS; RUNX3; Ras association (RalGDS/AF-6) domain family member 1; Ras association (RalGDS/AF-6) domain family member 2; Rb; Retinoic acid receptor responder (tazarotene induced) 1; Retinoic acid receptor, beta; Retinol binding protein 1, cellular; Runt-related transcription factor 3; S-adenosylmethionine; SAM; SFRP2; SFRP5; SHP1; SOCS-1; STAT3; SYK; Secreted frizzled-related protein 2; Secreted frizzled-related protein 5; Serine peptidase inhibitor, Kunitz type, 2; Spleen tyrosine kinase; Suppressor of cytokine signaling 1; TCF4; TET; TFPI2; TGF-β; TIMP metallopeptidase inhibitor 3; TIMP3; TNM; TP73; TSP1; Thrombospondin 1; Tissue factor pathway inhibitor 2; Transcription factor 4; Tumor Node Metastasis; Tumor protein p73; V-erb-a erythroblastic leukemia viral oncogene homolog 4; ZFP82 zinc finger protein; ZIC1; ZNF545; Zinc finger protein of the cerebellum 1; gastrointestinal endoscopy; glial cell derived neurotrophic factor; hDAB2IP; hMLH1; hepatocyte growth factor activator; latent membrane protein; mutL homolog 1; myelodysplastic syndromes; p15; p16; p21; p27; p53; p73; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; phosphoinositide 3-kinase (PI3K)/Akt; reactive oxygen species; retinoblastoma; signal transducer and activator of transcription-3; ten-eleven translocation; transforming growth factor-β; tumor protein p53; tumor protein p73; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Promoter Regions, Genetic
  • Proto-Oncogene Mas
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism


  • Histones
  • MAS1 protein, human
  • MicroRNAs
  • Neoplasm Proteins
  • Nucleosomes
  • Proto-Oncogene Mas
  • RNA, Untranslated
  • Tumor Suppressor Proteins