Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas

Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas
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DOI:
10.1002/ijc.21145
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发表时间:
2005-10
影响因子:
6.4
通讯作者:
Yan Zhang;Yoshiko Hiraishi;Hua Wang;K. Sumi;Y. Hayashido;S. Toratani;M. Kan;J. Sato;T. Okamoto
Yan Zhang;Yoshiko Hiraishi;Hua Wang;K. Sumi;Y. Hayashido;S. Toratani;M. Kan;J. Sato;T. Okamoto
中科院分区:
医学1区
文献类型:
--
作者:
Yan Zhang;Yoshiko Hiraishi;Hua Wang;K. Sumi;Y. Hayashido;S. Toratani;M. Kan;J. Sato;T. Okamoto

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在62%(44/71)的口腔鳞状细胞癌(OSCC)中观察到人FGFR 3b编码区2128位核苷酸的G → T突变,导致酪氨酸激酶结构域的Cys → Gly(G697 C)。免疫染色的FGFR 3b在正常上皮中的棘细胞的细胞质中被发现,并且FGFR 3b定位于非FGFR 3b突变OSCC的细胞质和细胞核中。在携带FGFR 3b突变的OSCC中,质膜上的FGFR 3b蛋白过度表达。证实了G697 CFGFR 3b的增强的酪氨酸激酶活性。我们的研究结果表明,G697 C是一种激活突变,导致组成型配体非依赖性FGFR 3b信号传导。该突变可能参与OSCC的进展,因此FGFR 3b编码序列可能对OSCC具有诊断或预后价值。© 2005 Wiley利斯公司
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.