Dear Sir,

We read with great interest the Letter to the Editor by Aubertin et al.1 in which they reported that 100% of 39 tested oral squamous cell carcinoma (OSCC) samples contained wild-type sequence in codon 697 of the FGF receptor 3 gene. These results appear to contradict our own finding that 62% of 71 tested OSCC samples possessed a somatic missense mutation, which resulted in a glycine to cysteine substitution at position 697 (G697C) of FGFR3.2 As we also found that this mutated form of FGFR3 had higher autophosphorylation activity than wild-type FGFR3, we suggested that FGFR3 and the G697C activating mutation might play an important role in the development of SCC in oral epithelia. As pointed out by Aubertin et al., the patient populations in these 2 studies were different: their OSCC patients were likely Caucasians from northeastern France while our patients were exclusively Japanese. We suspect that the discrepancy in our experimental results stem from these different patient populations. There may be ethnic, lifestyle or environmental factors, which are not found in northeastern France, that predispose OSCC patients in the Hiroshima area to develop tumors via a mechanism involving the G697C mutation. These potential variations in patient populations are reminiscent of somatic mutations in the epidermal growth factor receptor that rendered Japanese patients with nonsmall cell lung carcinoma generally more responsive to gefitinib (Iressa) than nonsmall cell lung carcinoma patients in the United States.3, 4 Our report and that of Aubertin et al. serve to emphasize that there are likely multiple mechanistic pathways leading to OSCC. We believe that a survey of 110 OSCC patients from 2 geographic areas is insufficiently large to determine whether or not FGFR3 G697C is a common oncogenic mutation in OSCC. However, for OSCC patients with G697C-positive tumors, this diagnosis may have prognostic value.

Yours sincerely,


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  • 1
    Aubertin J,Tourpin S,Janot F,Ahomadegbe J-C,Radvanyi F. Analysis of fibroblast growth factor receptor 3 G697C mutation in oral squamous cell carcinomas. Int J Cancer 2006; DOI 10.1002/ijc.22285.
  • 2
    Zhang Y,Hiraishi Y,Wang H,Sumi K-S,Hayashido Y,Toratani S,Kan M,Sato JD,Okamoto T. Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas. Int J Cancer 2005; 117: 1668.
  • 3
    Paez JG,Janne PA,Lee JC,Tracy S,Greulich H,Gabriel S,Herman P,Kaye FJ,Lindeman N,Boggon TJ,Naoki K,Sasaki H et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497500.
  • 4
    Lynch TJ,Bell DW,Sordella R,Gurubhagavatula S,Okimoto RA,Brannigan BW,Harris PL,Haserlat SM,Supko JG,Haluska FG,Louis DN,Christiani DC et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350: 212939.

Yan Zhang, Yoshiko Hiraishi, Hua Wang, Ken-Saku Sumi, Yasutaka Hayashido, Shigeaki Toratani, Mikio Kan, John Denry Sato, Tetsuji Okamoto.