Pathogenetic mechanisms in gastric cancer

Table 1 Genetic alterations in gastric cancer

Genes	Alterations	Function	Pathology	Prognosis	Ref.
Tumor suppressor genes
TP53	Mutation/LOH	Transcription factor	Both	Association with poor survival	[42,46,48,182]
APC	Mutation/ LOH	Signal transduction	Intestinal	Association with poor survival	[48,98,99]
CDHI	Mutations/LOH	Adhesion	Diffuse	Association with poor survival	[48,102,106,183,184]
hMLH1/hMSH2	Mutations	DNA mismatch repair	Both	Association with poor survival and microsatellite instability	[10,140,185]
p16	Mutations/LOH	Cell cycle	Both	LOH of p16 association with lymph metastasis	[48,136,186,187]
RIZ	Mutations/LOH	Nuclear histone/protein methyltransferase	-	Association with microsatellite instability	[188-190]
hMSH3	Mutations	DNA mismatch repair	-	Association with microsatellite instability	[191,192]
hMSH6	Mutations	DNA mismatch repair	-	Association with microsatellite instability	[191,192]
PTEN	Mutations/LOH	protein tyrosine phosphatases	Both	Association with TNM stage, lymph node metastasis and poor survival	[65,66,193,194]
bcl-2	LOH	Apoptosis inhibitor	Intestinal	Association with invasion depth and lymph node metastasis	[182,195]
DCC	LOH	Cell adhesion	Intestinal	Association with poor survival	[48,196]
NM23	LOH	Nucleoside diphosphate kinase	Both	Association with metastasis and poor survival	[197-199]
p21	Loss	Cell cycle	Both	Association with poor survival	[51]
FHIT	LOH	Purine metabolism	Both	Association with invasive depth and microsatellite instability	[200]
BRCA1	LOH	Genetic instability	Both	Association with poor survival	[201,202]
Oncogenes
β-Catenin	Mutations	Adhesion,	Intestinal	Association with poor survival and EBV-associated GC	[10,58,97]
		Signal transduction
BRAF	Mutations	Signal transduction	Both	Association with microsatellite instability	[71,203]
K-Ras	Mutations	Signal transduction	Intestinal	Association with poor prognosis and microsatellite instability	[57,71-73,204]
PIK3CA	Amplification	Signal transduction	Both	Association with poor survival	[55-58]
	Mutations
EGFR	Amplification	Growth factor receptor	Both	Association with poor survival	[57,81,205]
		Tyrosine kinases
ERBB2	Amplification	Growth factor Receptor	Intestinal	Association with poor survival	[68,81-85,205]
	Mutations	Tyrosine kinases
ERBB3	Overexpression	Growth factor receptor	Diffuse	Association with poor survival	[68,81,85]
		Tyrosine kinases
ERBB4	Amplification	Growth factor receptor	Both	Association with poor survival	[86]
		Tyrosine kinases
c-Met	Amplification	Growth factor receptor	Diffuse	Association with poor survival	[86,206]
KSAM	Amplification	Growth factor receptor	Diffuse	Association with poor survival	[207]
VEGF	Overexpression	Growth factor	Intestinal	Association with metastasis and poor survival	[153,154,208]
CD44	Amplification	Cell adhesion	Both	Association with metastasis and poor survival	[86,209]
PRL3	Amplification	Cell signaling molecules	Both	Association with metastasis and poor survival	[210,211]
c-Myc	Amplification	Transcription factor	Intestinal	Association with poor survival	[212,213]
Cyclin E	Amplification	Cell cycle regulator	Both	Association with poor survival	[208,214]

LOH: Loss of heterozygosity.