title: Mutations in components of the Wnt signaling pathway in adenoid cystic carcinoma.
abstract: The Wnt signaling pathway is essential for normal development and organogenesis. However, inappropriate activation of Wnt signaling, which results in the nuclear translocation of beta-catenin, is associated with the development of various types of neoplasm. In this study, we investigated possible mutations in the genes for components of this pathway, namely, CTNNB1 (the gene for beta-catenin), AXIN1, and APC, in adenoid cystic carcinoma, by PCR, analysis of single-strand conformational polymorphism, and sequencing. Among a total of 20 cases of adenoid cystic carcinoma, seven cases (35%) were associated with mutations in one or more of these three components. A mutation in CTNNB1 was detected in one case. Five cases, including the case with a mutation in CTNNB1, were associated with missense mutations in AXIN1. An aberration in the mutation cluster region of APC was detected in two cases. Mutations trended to be detected more frequently in adenoid cystic carcinoma with solid growth pattern than that with tubular and cribriform growth pattern. In the cases in which we detected mutations, it is possible that the presence of the abnormal products of the mutated genes resulted in the inappropriate activation of the Wnt signaling pathway to tumorigenesis and the growth of adenoid cystic carcinoma.
authors.affiliation: Department of Pathology, Faculty of Medicine, Oita University, Oita, Japan. daatom@med.oita-u.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Daa
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashima
authors.forename: Naomi
authors.initials: N
authors.lastname: Kaku
authors.forename: Masashi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D060466:Axin Protein; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012097:Repressor Proteins / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics; D051153:Wnt Proteins; D051176:beta Catenin
chemical_list: C555451:AXIN1 protein, human; D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D036341:Intercellular Signaling Peptides and Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin