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Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas
Author(s) -
Zhang Yan,
Hiraishi Yoshiko,
Wang Hua,
Sumi Kensaku,
Hayashido Yasutaka,
Toratani Shigeaki,
Kan Mikio,
Sato J. Denry,
Okamoto Tetsuji
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21145
Subject(s) - cytoplasm , mutation , mutant , biology , tyrosine kinase , tyrosine , cancer research , cell , microbiology and biotechnology , signal transduction , gene , biochemistry
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 G697C FGFR3b 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. © 2005 Wiley‐Liss, Inc.