Beta-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 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.
Rashid
A
A
Department of Pathology, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4095, USA.
Gao
Y T
YT
Bhakta
S
S
Shen
M C
MC
Wang
B S
BS
Deng
J
J
Fraumeni
J F
JF
Hsing
A W
AW
D000236:Adenoma / Q000235:genetics; D000368:Aged; D001483:Base Sequence; D001661:Biliary Tract Neoplasms / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010766:Phosphorylation; D017354:Point Mutation; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3