Frequent somatic mutations of the beta-catenin gene in intestinal-type gastric cancer

The increased level of cytoplasmic beta-catenin through the mutations to ei ther beta-catenin or adenomatous polyposis coli (APC) has been proposed as an important oncogenic step in various tumors. Gastric cancer showed freque nt genetic alterations of the APC gene, and the risk for gastric cancer in familial adenomatosus polyposis patients is 10 times higher than that in th e general population. These findings raise the possibility that mutations o f beta-catenin may also be associated with the development of gastric cance r. We detected seven somatic mutations in a portion of exon 3 encoding for the glycogen synthase kinase 3 beta phosphorylation consensus region of the beta-catenin gene in 43 gastric cancers. All of these mutations were misse nse mutations, of which five are in the highly conserved aspartic acid 32 a nd two are in serine 29; all of these seven mutations were detected exclusi vely in intestinal-type gastric cancers (7 of 26; 26.9%), but not in the di ffuse-type (0 of 17). We concluded that disruption of the APC/beta-catenin/ T cell factor-lymphoid enhancer binding factor pathway might play an import ant role especially in the development of intestinal-type gastric cancer.