Activation of the beta-catenin gene by interstitial deletions involving exon 3 as an early event in colorectal tumorigenesis

beta -Catenin has been identified as an oncogene in several tumors includin g colorectal cancers. beta -Catenin gene is activated by interstitial delet ions involving exon 3 in colorectal carcinomas of Japanese population, in c ontrast to amino acid substitutions detected among Caucasian population. Th e aim of this study was to examine the type and frequency of beta -catenin gene mutation during early stages of colorectal tumorigenesis. We screened 100 colorectal adenomas For somatic mutations in the beta -catenin gene by single-strand conformation polymorphism method, as well as polymerase chain reaction amplification. In cases with mutations, sequencing analyses and i mmunohistochemical staining were also performed. Somatic interstitial delet ions of 272-413 bp, each of which included all parts of tron 3, were detect ed in three tumors. However, no adenoma carried missense mutations. We conf irmed accumulation of aberrant beta -catenin protein in cytoplasm and nucle i of adenoma cells by immunohistochemical analysis. Our results suggested t hat activation of the beta -catenin gene by interstitial deletions involvin g exon 3 might be less frequent compared with frequent alterations of adeno matous polyposis coli (APC) gene, but could be an early event in colorectal tumorigenesis equivalent to APC gene alterations in the Japanese populatio n. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.