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 including colorectal cancers. beta-Catenin gene is activated by interstitial deletions involving exon 3 in colorectal carcinomas of Japanese population, in contrast to amino acid substitutions detected among Caucasian population. The 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 immunohistochemical staining were also performed. Somatic interstitial deletions of 272-413 bp, each of which included all parts of exon 3, were detected in three tumors. However, no adenoma carried missense mutations. We confirmed accumulation of aberrant beta-catenin protein in cytoplasm and nuclei of adenoma cells by immunohistochemical analysis. Our results suggested that activation of the beta-catenin gene by interstitial deletions involving exon 3 might be less frequent compared with frequent alterations of adenomatous polyposis coli (APC) gene, but could be an early event in colorectal tumorigenesis equivalent to APC gene alterations in the Japanese population.
Murata
M
M
Department of Surgery, Ikeda Municipal Hospital, 3-1-18 Jyonan, Ikeda-shi, 563-8510, Osaka, Japan. muratamasaru@mth.biglobe.ne.jp
Iwao
K
K
Miyoshi
Y
Y
Nagasawa
Y
Y
Yabu
M
M
Himeno
S
S
Imanishi
K
K
Ohsawa
M
M
Wada
H
H
Tominaga
S
S
Shimano
T
T
Kobayashi
T
T
Nakamura
Y
Y
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D015534:Trans-Activators; D051176:beta Catenin