β-Catenin mutations in biliary tract cancers: A population-based study in China

β-Catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both cadherin-mediated cell-cell adhesion and as a down-stream signaling molecule in the wingless/Wnt pathway. Activating mutations in exon 3 of the β-catenin gene, at the phosphorylation sites for ubiquitination and degradation of β-catenin, are present in a variety of cancers. Because alterations of the adenomatous polyposis coli (APC) gene are present in biliary tract cancers and the APC protein modulates levels of β-catenin, we evaluated the role of β-catenin in biliary tract cancer by sequencing the third exon of the β-catenin gene among 107 biliary tract cancers and 7 gallbladder adenomas from a population-based study in China, Point mutations of serine or threonine phosphorylation sites in exon 3 of β-catenin were present in 8 of 107 (7.5%) biliary tract cancers and 4 of 7 (57.1%) gallbladder adenomas. Mutations of β-catenin were more frequent in ampullary and gallbladder carcinomas than in bile duct carcinomas (P = 0.04) and in papillary adenocarcinomas than other histological types of carcinomas (P = 0.02). These results suggest that the molecular pathways of biliary tract neoplasms vary by anatomical subsite and histological subtype.