胃肠道间质瘤340例基因及靶向治疗分析

Analysis of gene and targeted therapy for 340 patients with gastrointestinal stromal tumor

目的探讨胃肠道问质瘤（GIST）患者的f晦床病理特征及c—kit、血小板源性生长受体a（PDGFRA）基因突变频率和突变类型。方法收集2012年1月至2014年12月手术切除并经术后病理证实的GIST患者340例临床病理资料及肿瘤组织标本，运用直接测序法检测组织标本中c-kit（外显子9、11、13和17）、PDGFRA基因（外显子12和18）的突变状态。结果340例GIST患者中，男性138例，女性192例；年龄37～81岁，中位年龄58岁。胃间质瘤178例（52．4％），十二指肠间质瘤21例（6．2％），小肠问质瘤82例（24．1％），结肠间质瘤10例（2．9％），直肠间质瘤15例（4．4％），胃肠道外（来自腹膜、系膜、腹膜后或附件）间质瘤30例（8．8％），肝脏（基因检测组织来自肝脏穿刺或手术切除标本）4例（1．2％）；340例GIST患者全部进行基因分型，总突变率89．4％（304／340），其中，c—kit突变276例（81．2％），PDGFRA突变28例（8．2％），野生型36例（10．6％）；125例患者的基因序列碱基突变检测中外显子11缺失突变49例，插入突变4例，错义突变12例；外显子9插入突变8例；外显子13错义突变1例；外显子17错义突变1例；外显子12同义突变24例；外显子18同义突变20例。结论c-kit基因外显子11为最常见的基因突变类型；基因突变类型与靶向药物的选择有一定的关系。

Objective To investigate clinical and pathological features of gastrointestinal stromal tumors, the frequency and type of mutation of c-kit and platelet-derived growth factor receptor α （PDGFRA） genes. Methods 340 patients underwent surgical resection and diagnosed as gastrointestinal stromal tumors by postoperative pathology from Junuary 2012 to December 2014 were enrolled, and their tumor tissues were collected. The direct sequencing method was applied to detect the mutation status of c-kit gene （exon 9, 11, 13 and 17） and PDGFRA gene （exonl2 and 18）. Results There were 138 males and 192 females, and their median age was 58 years old （37-81 years old）. There were 178 patients （52.4 %） with gastric stromal tumors, 21 cases （6.2 %） with duodenal stromal tumors, 82 cases （24.1%） with small intestinal stromal tumor, 10 cases （2.9 %） with colon stromal tumor, 15 cases （4.4 %） with rectal stromal tumors, 30 cases （8.8 %） with parenteral stromal tumor （from the peritoneum, mesentery, retroperitoneum or attachment）, 4 cases （1.2 %） of liver tissues （gene detection tissues from the liver biopsy or surgical resection specimens）. In the mutation analysis of all 340 patients with gastrointestinal stromal tumor, the total mutation rate was 89.4 % （304/340）, including 81.2 % （276 cases） of c-kit, 8.2 % （28 cases） of PDGFR and 10.6 % （36 cases） of wild type. Among 125 cases underwent the detection of the gene mutation sequences, there were 49 cases of exonl 1 deletion mutation, 4 cases of exonl 1 insertion mutation, 12 cases of exonl 1 missense mutation, 8 cases of exon9 insertion mutation, 1 case of 3xon13 missense mutation, 1 case of exonl7 missense mutation, 24 cases of exonl2 synonymous mutation and 20 cases of exonl8 synonymous mutation. Conclusions Gene detection is becoming more and more obvious in predicting the therapeutic effect of molecular targeted therapy, the mechanism of drug resistance and the clinical treatment, c-kit exonl 1 mutation is one of the most common gene mutation types related to the choice of targeted medicine.