Molecular and biological analysis of carcinoma of the small intestine: beta-catenin gene mutation by interstitial deletion involving exon 3 and replication error phenotype

The genetic mechanisms of carcinomas of the small intestine are not well un derstood. We report the results of analysis of genetic alterations in a cas e of small intestinal carcinoma. A tumor in the terminal ileum was resected in a 59-yr-old woman. Histologically, the tumor was classified as well-dif ferentiated adenocarcinoma. We screened for genetic alterations in adenomat ous polyposis coli (APC), beta-catenin, K-ras, and p53 genes, as well as mi crosatellite instability, which are known to be involved in colorectal tumo rigenesis. The tumor exhibited somatic interstitial deletion of 425-bp, whi ch included the entire exon 3 in beta-catenin gene. Immunohistochemical sta ining confirmed accumulation of aberrant beta-catenin protein in the cytopl asm and nuclei of the malignant tissue. Furthermore, a frameshift mutation in the transforming growth factor beta receptor type II gene with replicati on error phenotype was detected in the tumor DNA. In contrast, no genetic a lterations were found in the APC, K-ras, and p53 genes. Our results suggest ed that both beta-catenin gene mutation and replication error phenotype mig ht contribute to carcinogenesis of the small intestinal tumor in our case. This is the first report that activation of beta-catenin gene by somatic ge ne mutation is involved in the development of carcinoma of the small intest ine. (Am J Gastroenterol 2000;95:1576-1580. (C) 2000 by Am. Cell. of Gastro enterology).