Fibroblast growth factor receptor 4 mutation and polymorphism in Japanese lung cancer

We investigated the FGFR4 mutation status at the kinase domain and FGFR4 single nucleotide polymorphism (SNP) at codon 388 in surgically treated non-small cell lung cancer (NSCLC) cases. The presence or absence of FGFR4 mutations of kinase domains was analyzed by direct sequences (n=147), and the presence of FGFR4 Arg388 allele was analyzed by genotyping assay using LightCycler hybridization probes (n=387). FGFR4 mutations were not present in our lung cancer patients. In 61.8% of patients, homo- or heterozygous Arg388 allele was present. No correlation existed between the FGFR4 genotype and clinicopathological features such as gender, smoking status and pathological subtypes. EGFR mutation status was not correlated with the FGFR4 genotype of lung cancers. In node-negative patients, the FGFR4 genotype was not correlated with disease outcome, while in the node-positive patients FGFR4 Arg388 was significantly associated with worse survival. This association was not attributed to patient response to adjuvant chemotherapy. Therefore, the role of FGFR4 polymorphism is a prognostic marker for advanced NSCLC in Japanese patients.