title: Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations.
abstract: Among 222 primary colorectal cancers we examined, 58 showed no detectable APC mutations by the protein truncation test. We screened those 58 tumors for somatic mutations in the beta-catenin gene. Although amino acid substitutions in serine or threonine residues in exon 3 had been reported, we found no such mutations; however, in seven tumors, we detected somatic interstitial deletions of 234-760 bp, each of which included all or part of exon 3. Short nucleotide sequences at both ends of each deletion were either identical or complementary, indicating that repeated or inversely repeated sequences were involved in the somatic rearrangements. Reverse transcription-PCR experiments using RNAs isolated from three of these seven tumors detected transcripts that lacked exon 3, in addition to the normal transcript. In one of these cases, we confirmed accumulation of aberrant beta-catenin protein in cytoplasm and nuclei of cancer cells by Western and immunohistochemical analyses. This result suggested that, in the absence of a peptide encoded by exon 3, beta-catenin is stabilized and has a dominant oncogenic effect on colorectal tumorigenesis.
authors.affiliation: Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Suita City, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Iwao
authors.forename: S
authors.initials: S
authors.lastname: Nakamori
authors.forename: M
authors.initials: M
authors.lastname: Kameyama
authors.forename: S
authors.initials: S
authors.lastname: Imaoka
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita
authors.forename: T
authors.initials: T
authors.lastname: Fukui
authors.forename: S
authors.initials: S
authors.lastname: Ishiguro
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Miyoshi
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D006801:Humans; D017384:Sequence Deletion; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin