Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas

Authors

  • Yan Zhang,

    1. Department of Molecular Oral Medicine and Maxillofacial Surgery, Div. of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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    • The first two authors contributed equally to this work.

  • Yoshiko Hiraishi,

    1. Department of Molecular Oral Medicine and Maxillofacial Surgery, Div. of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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    • The first two authors contributed equally to this work.

  • Hua Wang,

    1. Department of Molecular Oral Medicine and Maxillofacial Surgery, Div. of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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  • Ken-saku Sumi,

    1. Department of Molecular Oral Medicine and Maxillofacial Surgery, Div. of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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  • Yasutaka Hayashido,

    1. Department of Molecular Oral Medicine and Maxillofacial Surgery, Div. of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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  • Shigeaki Toratani,

    1. Department of Molecular Oral Medicine and Maxillofacial Surgery, Div. of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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  • Mikio Kan,

    1. Zeria Pharmaceutical Co. Ltd., Central Research Laboratories, Saitama, Japan
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  • J. Denry Sato,

    1. Marine Cell Line and Stem Cell Program, Mount Desert Island Biological Laboratory, Salisbury Cove, ME, USA
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  • Tetsuji Okamoto

    Corresponding author
    1. Department of Molecular Oral Medicine and Maxillofacial Surgery, Div. of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
    • Department of Molecular Oral Medicine & Maxillofacial Surgery, Div. of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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    • Fax: +81-82-257-5669.


Abstract

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. © 2005 Wiley-Liss, Inc.

Ancillary