270例胃肠间质瘤基因突变谱及与临床病理特征关系

Gene mutation spectrum of 270 patients with gastrointestinal stromal tumor and its association with clinicopathological features

目的 :分析研究270例胃肠间质瘤(gastrointestinal stromal tumor,GIST)患者c-kit及血小板源性生长因子受体α(platelet-derived growth factor receptorα,PDGFRA)基因突变特点及与临床病理特征的关系。方法 :回顾性收集2016年6月至2019年1月重庆医科大学附属第一医院收治的270例GIST患者基因检测结果和临床病理资料,分析两者之间的关系。结果 :(1)270例患者中220例检测到c-kit突变,突变最常发生于11号外显子,其次为9号外显子。9号外显子均为A502-Y503重复突变。11号外显子主要为缺失突变和点突变,最常发生于557~560位点。7例PDGFRA突变中以D842V突变最常见。(2)c-kit 11突变中点突变和混合突变发生在胃上的概率小于其他类型突变(P=0.022)。c-kit 11突变患者中大于50岁的频率高于其他c-kit突变(P=0.040)。c-kit 9突变发生在小肠上的频率大于其他突变(P=0.000)。PDGFRA突变与野生型患者核分裂象<5/50 HPF的比例大于c-kit突变的患者(P=0.027)。c-kit突变患者CD117阳性率大于PDGFRA突变与野生型(P=0.000)。野生型患者平滑肌肌动蛋白(smooth muscle actin,SMA)阳性率高于突变型(P=0.002)。结论:GIST患者发生c-kit/PDGFRA突变的频率高,且突变位点、类型多样与临床病理特征关系密切,是GIST患者个体化治疗的重要依据。

Objective:To investigate the feature of c-kit and platelet-derived growth factor receptorα(PDGFRA)gene mutation in 270 patients with gastrointestinal stromal tumor(GIST),as well as its association with clinicopathological features.Methods:The gene detection result and clinicopathological data of 270 GIST patients,who underwent treatment in our hospital from June 2016 to January 2019,were collected retrospectively.Results:Among 270 patients,220 patients had c-kit mutations which were mainly occurred in exon 11,and then exon 9.Multimutation of A502-Y503 was the unique genotype for exon 9.Deletion mutation and point mutation were the most common mutations in c-kit exon 11,which mainly occurred in location of 557-560.Among seven patients with PDGFRA mutation,D842 V mutation in exon 18 was the most common type.Among all c-kit 11 mutations,the rate of point mutation or mixed mutations occurred in the stomach was lower than that of other mutation types(P=0.022).In patients with c-kit 11 mutations,the frequency of patients who were older than 50 years was more than other c-kit exon mutations(P=0.040).The rate of c-kit exon 9 mutation in the small intestine was higher than other mutations(P=0.000).The rate of mitotic count<5/50 HPF in patients with PDGFRA mutation and wild type was higher than that in c-kit mutation patients(P=0.027).CD117 positive rate in c-kit mutation patients was significantly higher than that in PDGFRA mutation and wild type patients(P=0.000).SMA positive rate in wild type patients was higher than that in mutation patients(P=0.002).Conclusion:GIST patients have high frequency to experience c-kit/PDGFRA;mutation locations and types are closely correlated with clinicopathological features,which also are important judgements for individual treatment.