Mutational analysis of Wnt signaling molecules in ameloblastoma with aberrant nuclear expression of β-catenin

• Published in: Journal of oral pathology & medicine 2008-10, Vol.37 (9), p.565-570
• Main Authors: Tanahashi, Jin, Daa, Tsutomu, Yada, Naomi, Kashima, Kenji, Kondoh, Yoshiyuki, Yokoyama, Shigeo
• Format: Article
• Language: English
• Subjects: ameloblastoma; Ameloblastoma - genetics; Ameloblastoma - metabolism; APC; AXIN; beta Catenin - metabolism; Biological and medical sciences; Cell Nucleus - metabolism; Cyclin D1 - genetics; Cyclin D1 - metabolism; Dentistry; DNA Mutational Analysis; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Gene Expression Regulation, Neoplastic; Humans; Jaw Neoplasms - genetics; Jaw Neoplasms - metabolism; Medical sciences; Mutation, Missense; Otorhinolaryngology. Stomatology; Signal Transduction; Tumors; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt signaling pathway; β-catenin
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/j.1600-0714.2008.00645.x

Background:  To clarify the genetic background of ameloblastoma, expression of β‐catenin, and mutational status of genes involved in Wnt signaling pathway were investigated. Methods:  We analyzed β‐catenin and cyclin D1 in 18 cases of ameloblastoma by immunohistochemical staining, and searched for mutations in CTNNB1 (gene for β‐catenin), APC, AXIN1, and AXIN2 by polymerase chain reaction (PCR) and direct sequencing method. Result:  We detected membranous and occasionally cytoplasmic expression of β‐catenin in 16 of 18 cases (89%), and nuclear expression of β‐catenin principally in the peripheral columnar cells in 11 of 18 cases (61%). In nine of the 18 cases (50%), we detected the expression of cyclin D1 principally in the peripheral columnar cells. However, there was no correlation between nuclear expressions of β‐catenin and cyclin D1. No missense mutations were found in CTNNB1, APC, AXIN1, and AXIN2 in all cases except for silent mutation and already‐known single nucleotide polymorphism. Conclusion:  Mutations in CTNNB1, APC, AXIN1, and AXIN2 are not implicated in nuclear accumulation of β‐catenin, and that the expression of cyclin D1 is accelerated independently of β‐catenin in ameloblastomas. Other Wnt signaling members or alternative pathways involved in the degradation of β‐catenin should be subject of further investigation.