NSCLC罕见EGFR双突变继发KRAS突变1例报道并文献复习

Acquired KRAS mutation after rare double mutation of EGFR in NSCLC:1 case report and literature review

目的探讨非小细胞肺癌(NSCLC)中表皮生长因子受体(EGFR)基因罕见双突变病例的临床病理学特征及治疗意义。方法对1例EGFR基因罕见双突变,并在使用酪氨酸激酶抑制剂(TKI)后继发KRAS基因突变的肺腺癌病例进行回顾,同时进行相关文献复习,基因检测分别应用ARMS-PCR、二代测序(NGS)及Sanger测序法。结果患者因头部、右肩部、右季肋部、左臀部包块3个月就诊,穿刺活检示转移腺癌,考虑来自肺,1年后左前臂发现新转移灶,活检NGS检测示EGFR L858R及KRAS G12D突变;对3次活检组织行Sanger测序发现EGFR基因均为L858R合并R776H双突变。结论EGFR L858R合并R776H突变为罕见双突变,靶向治疗后获得性KRAS基因突变相关报道亦少见。

Objective To investigate the clinicopathological features and therapeutic significance of rare double mutations of epidermal growth factor receptor(EGFR)gene in non-small cell lung cancer(NSCLC).Methods A rare case of double mutation of EGFR in lung adenocarcinoma was retrospectively analyzed whose KRAS gene mutation was acquired after using tyrosine kinase inhibitor(TKI).The related literatures were reviewed.The gene mutations were detected using ARMS-PCR,next generation sequencing(NGS)and Sanger sequencing respectively.Results A 68-year-old female presented with multiple masses of head,right shoulder,right quarte rib and left hip for 3 months.Puncture biopsy showed metastatic adenocarcinoma from the lung.One year later,new metastases were found in the left forearm,EGFR L858R and KRAS G12D mutations were detected by using NGS from biopsy samples.At last,all the three biopsies were tested by Sanger sequencing,it was confirmed that L858R and R776H double mutations of EGFR gene were found in all of three samples.Conclusion EGFR L858R combined with R776H mutation is a rare double mutation in lung adenocarcinoma,also acquired mutation of KRAS gene after targeted therapy is rarely reported.