A novel somatic FGFR3 mutation in primary lung cancer.

The recent discovery of mutations and fusions of oncokinase genes in a subset of lung cancers (LCs) is of considerable clinical interest, since LCs containing such mutations or fusion transcripts are reportedly sensitive to kinase inhibitors. To better understand the role of the recently identified fibroblast growth factor receptor 3 (FGFR3) mutations and fusions in pulmonary carcinogenesis, we examined 214 LCs for mutations in the mutation cluster region of the FGFR3 gene using sequencing analysis. We also examined 190 LCs for the FGFR3-TACC3 and FGFR3-BAIAP2L1 fusion transcripts using reverse transcription-polymerase chain reaction (RT-PCR) analysis. Although the expression of FGFR3-TACC3 and FGFR3-BAIAP2L1 fusion transcripts was not detected in any of the carcinomas, somatic FGFR3 mutations were detected in two (0.9%) LCs. The two mutations were the same, i.e., p.R248H. That was a novel mutation occurring in the same codon as p.R248C, for which an oncogenic potential has previously been shown. Increased FGFR3 expression was shown in the two LCs containing the FGFR3 p.R248H mutation using qPCR. Histologically, both carcinomas were squamous cell carcinomas, therefore the incidence of the FGFR3 mutation among the squamous cell carcinoma cases was calculated as 3.2% (2/63). When we examined other co-occurring genetic abnormalities, one case exhibited a p53 p.R273C mutation, while the other case exhibited PIK3CA and SOX2 amplifications. The above results suggest that an FGFR3 p.R248H mutation is involved in the carcinogenesis of a subset of LCs and may contribute to the elucidation of the characteristics of FGFR3 mutation-positive LCs in the future.