Mutations in components of the Wnt signaling pathway in gastric cancer.
OBJECTIVE
To explore the contribution of AXIN1, AXIN2 and beta-catenin, components of Wnt signaling pathway, to the carcinogenesis of gastric cancer (GC), we examined AXIN1, AXIN2 exon7 and CTNNB1 (encoding beta-catenin) exon3 mutations in 70 GCs.


METHODS
The presence of mutations was identified by polymerase chain reaction (PCR)-based denaturing high-performance liquid chromatography and direct DNA sequencing. Beta-catenin expression was detected by immunohistochemical analysis.


RESULTS
Among the 70 GCs, 5 (7.1%) had mutations in one or two of these three components. A frameshift mutation (1 bp deletion) in exon7 of AXIN2 was found in one case. Four cases, including the case with a mutation in AXIN2, had frameshift mutations and missense mutations in AXIN1. Five single nucleotide polymorphisms (SNPs), 334 C>T, 874 C>T, 1396 G>A, 1690 C>T and 1942 T>G, were identified in AXIN1. A frameshift mutation (27 bp deletion) spanning exon3 of CTNNB1 was observed in one case. All four cases with mutations in AXIN1 and AXIN2 showed nuclear beta-catenin expression.


CONCLUSIONS
These data indicate that the mutations in AXIN1 and AXIN2 may contribute to gastric carcino-genesis.
Pan
Kai-Feng
KF
Department of Cancer Epidemiology, Peking University School of Oncology and Beijing Cancer Hospital & Institute, Beijing, China.
Liu
Wan-Guo
WG
Zhang
Lian
L
You
Wei-Cheng
WC
Lu
You-Yong
YY
D060466:Axin Protein; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics
C555451:AXIN1 protein, human; C491761:AXIN2 protein, human; D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D012097:Repressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin