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

摘要:

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 receptor α，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：①270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。②c-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。

Abstract:

Objective：To investigate the feature of c-kit and platelet-derived growth factor receptor α（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 oc－curred 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，D842V 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 expe－rience c-kit/PDGFRA；mutation locations and types are closely correlated with clinicopathological features，which also are impor－tant judgements for individual treatment.