Frequent Mutations in the β-Catenin Gene in Cholangiocarcinoma

The molecular pathogenesis of cholangiocarcinoma (CC) remains unclear. β-Catenin functions in both intercellular adhesion and signal transduction. As a signaling molecule, mutations in exon 3 of the β-catenin gene encoding the regions phosphorylated by glycogen synthase kinase (GSK)-3β stabilize this protein in cytoplasm. Subsequently, accumulated β-catenin protein translocates to nuclei and up-regulates the transcriptional activity of genes involved in oncogenesis. Recently, mutations in exon 3 of the β-catenin gene were detected in various carcinomas. Using polymerase chain reaction (PCR)-single-strand conformational polymorphism (SSCP) analysis, direct sequencing and subcloning-sequencing, we investigated mutations of exon 3 of the β-catenin gene in CC. Mutations were found in 26 out of 33 (78.8%) CC tumor samples. All of the mutations were heterozygous 1-base deletions at codon 15, resulting in a stop codon at codon 46. This is the first study demonstrating the presence of β-catenin gene mutations in CC. However, it was suggested that this mutation might not be involved in deregulation of β-catenin signaling, because no correlation was observed between the β-catenin mutation and immunolocalization of β-catenin protein.