Analysis of fibroblast growth factor receptor 3 G697C mutation in oral squamous cell carcinomas

Dear Sir, Zhang et al. recently reported an activating mutation of the receptor tyrosine kinase fibroblast growth factor receptor 3 in 62% of 71 oral squamous cell carcinomas (OSCC). More than 300,000 new cases of OSCC are diagnosed annually, worldwide. This aggressive epithelial cancer is associated with severe morbidity and a 5-year survival rate of less than 50%, despite advances in surgical treatment, radiotherapy and chemotherapy. Indeed the high rates of morbidity and mortality associated with this devastating disease have not improved in decades. Agents for the molecular targeting of OSCC treatment are urgently needed. The discovery of an activating mutation in a receptor tyrosine kinase (RTK) may represent a major advance towards the identification of new therapies, as RTKs have recently been successfully used as targets for cancer treatment. FGFRs are involved in cell growth, differentiation and migration and plays important roles in embryogenesis and tissue homeostasis. FGFR3 exists in 2 mutually exclusive isoforms: FGFR3b, which is the main form expressed in epithelial cells and FGFR3c, the main form expressed in chondrocytes. Activating somatic mutations in exons 7, 10 and 15 of FGFR3 have been reported in several types of cancer: multiple myeloma, bladder and cervical carcinomas. Such mutations are very frequent in bladder carcinoma (about 50% of all cases), and rarer in multiple myeloma and cervical carcinomas. No such mutations have been found in OSCC. Zhang et al. previously reported that FGFR3b is expressed in cells derived from OSCC. In their recent publication, these authors reported that 62% (44 of 71) of OSCC contain the same somatic missense mutation at codon 697 of the FGFR3 gene