Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas.
A G to T mutation at nucleotide position 2128 in the human FGFR3b coding region resulting in a Cys for Gly substitution (G697C) in the tyrosine kinase domain was observed in 62% (44/71) of oral squamous cell carcinomas (OSCC) examined. Immunostained FGFR3b was found in the cytoplasm of prickle cells in normal epithelia, and FGFR3b was localized in the cytoplasm and nucleus in non-FGFR3b mutant OSCC. Overexpressed FGFR3b protein on plasma membranes was noted in OSCC bearing the FGFR3b mutation. Enhanced tyrosine kinase activity of G697CFGFR3b was confirmed. Our results indicate that G697C is an activating mutation causing constitutive ligand-independent FGFR3b signaling. This mutation may be involved in the progression of OSCC and thus the FGFR3b coding sequence may have diagnostic or prognostic value for OSCC.
Zhang
Yan
Y
Department of Molecular Oral Medicine and Maxillofacial Surgery, Div. of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Hiraishi
Yoshiko
Y
Wang
Hua
H
Sumi
Ken-saku
KS
Hayashido
Yasutaka
Y
Toratani
Shigeaki
S
Kan
Mikio
M
Sato
J Denry
JD
Okamoto
Tetsuji
T
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3