Elsevier

Clinica Chimica Acta

Volume 424, 23 September 2013, Pages 53-65
Clinica Chimica Acta

Invited critical review
Gene methylation in gastric cancer

https://doi.org/10.1016/j.cca.2013.05.002Get rights and content
Under a Creative Commons license
open access

Highlights

  • An overview of the literature reporting genes hypermethylated in gastric cancer.

  • Gene methylation predicts poor clinical outcomes in gastric cancer.

  • Gene methylation represents a potential target for detection and diagnosis of 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.

Abbreviations

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

Keywords

Gastric cancer
Epigenetics
Gene methylation
Biomarkers
Clinical outcomes

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