尿路上皮癌FGFR基因变异初探

Fibroblast growth factor receptor gene alterations in urothelial carcinoma:a preliminary study

目的探讨尿路上皮癌(UC)成纤维细胞生长因子受体(FGFR)基因变异特征,为筛选潜在获益于FGFR抑制剂的目标人群和制定检测策略提供参考。方法收集40例存档的甲醛固定石蜡包埋的尿路上皮癌组织标本,采用新一代测序技术分析FGFR基因变异。结果在40例尿路上皮癌样本中检出FGFR基因变异10例(25.0%,10/40),包括FGFR2 M538I突变1例、FGFR3 S249C突变4例、FGFR3 R248C突变2例、FGFR3 Y373C突变1例、FGFR3 G548R突变1例及FGFR3 Y373C/FGFR4 K186M双突变1例。其中G548R和K186M突变未见报道。结论尿路上皮癌患者中存在特殊的FGFR变异位点,生物学意义待明确,有必要扩大样本量进一步研究。

Objective To investigate fibroblast growth factor receptor(FGFR)gene alteration in urothelial carcinoma(UC)patients which will contribute to identifying beneficiaries from FGFR inhibitors and develop gene detection strategies.Methods Total 40 formalin-fixed paraffin-embedded tissue samples from urothelial carcinoma were analyzed for FGFR gene abnormality using next generation sequencing.Results FGFR gene mutations were found in 10 of 40 cases(25.0%),including 1 FGFR2 M538I,4 FGFR3 S249C,2 FGFR3 R248C,1 FGFR3 Y373C,1 FGFR3 G548R and 1 FGFR3 Y373C/FGFR4 K186M double mutation cases.Among FGFR-mutant tumors,UC with G548R or K186M mutation had not been reported to date.Conclusion Urothelial carcinoma harbores rare FGFR variants,which epidemiology and biological significance needs to be elucidated and further explored in a larger study cohort.