Mutational analysis of Wnt signaling molecules in ameloblastoma with aberrant nuclear expression of beta-catenin.
BACKGROUND
To clarify the genetic background of ameloblastoma, expression of beta-catenin, and mutational status of genes involved in Wnt signaling pathway were investigated.


METHODS
We analyzed beta-catenin and cyclin D1 in 18 cases of ameloblastoma by immunohistochemical staining, and searched for mutations in CTNNB1 (gene for beta-catenin), APC, AXIN1, and AXIN2 by polymerase chain reaction (PCR) and direct sequencing method.


RESULTS
We detected membranous and occasionally cytoplasmic expression of beta-catenin in 16 of 18 cases (89%), and nuclear expression of beta-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 beta-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.


CONCLUSIONS
Mutations in CTNNB1, APC, AXIN1, and AXIN2 are not implicated in nuclear accumulation of beta-catenin, and that the expression of cyclin D1 is accelerated independently of beta-catenin in ameloblastomas. Other Wnt signaling members or alternative pathways involved in the degradation of beta-catenin should be subject of further investigation.
Tanahashi
Jin
J
Department of Pathology, Faculty of Medicine, Oita University, Yufu-shi, Japan.
Daa
Tsutomu
T
Yada
Naomi
N
Kashima
Kenji
K
Kondoh
Yoshiyuki
Y
Yokoyama
Shigeo
S
D000564:Ameloblastoma / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007573:Jaw Neoplasms / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1