Review
Copyright ©2006 Baishideng Publishing Group Co.
World J Gastroenterol. Mar 21, 2006; 12(11): 1671-1680
Published online Mar 21, 2006. doi: 10.3748/wjg.v12.i11.1671
Table 1 Molecular alteration in the process of gastric carcinogenesis
Molecules Major alterationsComments Category
p53Mutation, LOHReported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions.Tumor suppressor
APCMutation, LOHReported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions.Tumor suppressor
DCCLOHReported in intestinal-type adenocarcinomas. Related to cell adhesionTumor suppressor
CDH1MutationReported in diffuse-type adenocarcinomas.Tumor suppressor
β-cateninMutationReported in intestinal-type adenocarcinomas.Tumor suppressor
FhitLOH or deletion at chr. 3p14.2Reported in diffuse-type and, in less frequency, intestinal-type adenocarcinomas, as well as some precancerous lesions.Tumor suppressor
RUNX3HypermethylationRelated to TGF-β/SMAD signaling.Tumor suppressor
K-rasMutationReported in intestinal-type adenocarcinomas. An element in signal transduction regulating cell proliferation, etc..Oncogene
bcl-2LOHReported in intestinal-type adenocarcinomas. Anti-apoptotic factor.Oncogene
c-metAmplificationReported in diffuse-type and intestinal-type adenocarcinomas. The HGF receptor / tyrosine-kinase. Upregulation without mutation is also reported after mucosal injury.Oncogene / Growth stimulus
c-erbB2AmplificationReported in intestinal-type adenocarcinomas. One of receptor-tyrosine kinases for EGF-family proteins.Oncogene / Growth stimulus
Cyclin EAmplificationReported in diffuse-type and intestinal type adenocarciomas.Cell cycle regulator
K-samAmplificationReported in diffuse-type adenocarcinomas. One of bFGF receptor family proteins, FGFR2.Oncogene
Mismatch repair (MMR) genesSilencing due to hypermethylationReported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions. A possible source of mutations of other genes involving gastric carcinogenesis.Determinants of microsatelite instability (MSI)
MMR genesMutationReported in diffuse-type and intestinal-type adenocarcinomas. There are conflicting data suggesting that mucosa with intestinal metaplasia is prone to and resistant to MSI.Determinants of MSI
EGFROverexpressionReported in diffuse-type and intestinal-type adenocarcinomas.Growth stimulus
EGFOverexpressionReported in diffuse-type and intestinal-type adenocarcinomas.Growth stimulus
TGF-αOverexpressionReported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions. Another EGF-family protein.Growth stimulus
VEGFOverexpressionReported in diffuse-type and intestinal-type adenocarcinomas.Angiogenic factor
iNOSOverexpressionReported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions and mucosa with H. pylori.Enzyme
COX-2OverexpressionReported in diffuse-type and intestinal-type adenocarcinomas, as well as some precancerous lesions and mucosa with H. pylori. Cytokines and growth factors are possible inducer of COX-2.Enzyme
ODCOverexpressionReported earlier in gastritis.Enzyme
TelomeraseActivatedEnlongs telomere and prevents cell senescence.Enzyme
CDXsOverexpressionReported in diffuse-type and intestinal-type adenocarcinomas, as well as precancerous lesions. Is involved in intestinal metaplasia.Transcription factor
Ets1OverexpressionA transcription factor involving angiogenesis.Transcription factor
NF-κBOverexpressionA transcription factor regulating expression of proinflammatory cytokines, chemokines, iNOS and COX-2.Transcription factor
Sp-1OverexpressionReported in diffuse-type and intestinal-type adenocarcinomas.Transcription factor
SC-1OverexpressionReported in diffuse-type adenocarcinomas.Apoptosis receptor
Fas/CD95OverexpressionReported in diffuse-type adenocarcinomas.Apoptosis receptor
E-cadherinMutationReported in diffuse-type and intestinal-type adenocarcinomas.Cell adhesion
CD44Splicing variantReported in diffuse-type and intestinal-type adenocarcinomas.Cell adhesion
GastrinElevation in serumElevation of amidated gastrin is reported. Transactivates EGF-family proteins.Gut hormone