Cancer Res  1998 Mar 1;58(5):1021-6 

Activation of the beta-catenin gene by interstitial deletions involving exon 3
in primary colorectal carcinomas without adenomatous polyposis coli mutations.

Iwao K, Nakamori S, Kameyama M, Imaoka S, Kinoshita M, Fukui T, Ishiguro S,
Nakamura Y, Miyoshi Y.

Department of Medical Genetics, Biomedical Research Center, Osaka University
Medical School, Suita City, Japan.

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.

PMID: 9500465 [PubMed - indexed for MEDLINE]