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

beta-Catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless/Wnt pathway. Activating mutations in exon 3 of the beta-catenin gene, at the phosphorylation sites for ubiquitinat...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001-04, Vol.61 (8), p.3406-3409
Main Authors: RASHID, Asif, GAO, Yu-Tang, BHAKTA, Sapna, SHEN, Ming-Chang, WANG, Bing-Sheng, JIE DENG, FRAUMENI, Joseph F, HSING, Ann W
Format: Article
Language:English
Subjects:
Adenoma - genetics
Aged
b-catenin
Base Sequence
beta Catenin
Biliary Tract Neoplasms - genetics
Biological and medical sciences
Calcium-Calmodulin-Dependent Protein Kinases - genetics
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Carcinoma - genetics
Case-Control Studies
China
Cytoskeletal Proteins - genetics
Exons
Female
Gallbladder Neoplasms - genetics
Gastroenterology. Liver. Pancreas. Abdomen
Glycogen Synthase Kinase 3
Humans
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Middle Aged
Molecular Sequence Data
Mutation, Missense
Phosphorylation
Point Mutation
Trans-Activators
Tumors
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Summary:beta-Catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless/Wnt pathway. Activating mutations in exon 3 of the beta-catenin gene, at the phosphorylation sites for ubiquitination and degradation of beta-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 beta-catenin, we evaluated the role of beta-catenin in biliary tract cancer by sequencing the third exon of the beta-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 beta-catenin were present in 8 of 107 (7.5%) biliary tract cancers and 4 of 7 (57.1%) gallbladder adenomas. Mutations of beta-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.
ISSN:0008-5472
1538-7445