目的    探讨胃肠间质瘤病人的临床病理特征及c-kit/血小板源性生长受体α（PDGFRA）基因突变频率和突变类型。方法    收集2002年1月至2011年10月于北京大学肿瘤医院就诊并经病理组织学确诊的660例胃肠间质瘤病人的临床病理资料及肿瘤组织标本，运用直接测序方法检测组织标本中c-kit（外显子9、11、13和17）、PDGFRA基因（外显子12和18）的突变状态，统计学分析基因型与临床病理特征的相关性。结果    660例胃肠间质瘤病人中，男389例（58.9%），女271例（41.1%）。中位年龄56（15~82）岁。原发部位以胃（37%）和小肠（35%）为主，转移部位以肝脏及腹腔最常见。酪氨酸激酶受体(CD117)阳性率95.0%，DOG1阳性率88.1%。360例病人接受基因突变检测，其中c-kit基因外显子11突变241例(66.9%)，外显子9突变43例(11.9%)，外显子13突变6例（1.7%），外显子17突变4例（1.1%），PDGFRA基因外显子12突变1例（0.3%），外显子18突变7例（1.9%），野生型病人58例（16.2%）；c-kit外显子9突变主要见于小肠，而PDGFRA12/18突变主要见于胃；基因突变频率与肿瘤大小与和分裂像未见相关性。结论    胃肠间质瘤最常发生在胃和小肠；c-kit基因外显子11为最常见的基因突变类型；基因突变类型与原发部位相关。

The clinicopathologic features and gene mutation status of gastrointestinal stromal tumor (with the analysis of 660 cases of patients)        DANG Yun-zhi, GAO Jing, LI Jian, et al. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI Oncology, PekingUniversity Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142, China
Corresponding author: SHEN Lin, E-mail:lin100@medmail.com.cn
Abstract    Objective    To investigate the clinical and pathological features in patients with gastrointestinal stromal tumors (GISTs), focusing on the mutation status of c-kit and PDGFRA. Methods    Data and tumor samples of 660 patients diagnosed and treated as GISTs in Peking University Cancer Hospital from January 2002 to October 2011 were collected. Mutation status of c-kit (exons 9, 11, 13 and 17)、PDGFRA (exons 12 and 18) were detected by direct sequencing. Statistical tool was used to analyze the relationship between gene mutation types and pathological features. Results    389(58.9%) men and 271(41.4%) women, median age 56 years (15-82 years), were involved. The predominant sites of tumor origin were from stomach (37%) and small intestine (35%)，while liver and peritoneum were the most commons sites of metastasis. 95.0% and 88.1% of GIST patients were positive for the CD117 and DOG1 antigens, respectively. A total number of 360 GIST patients were genotyped, with 241 (66.9%), 43 (11.9%), 6 (1.7%), 4 (1.1%), 1 (0.3%) and 7 (1.9%) having c-kit exons 11, 9, 13, 17, PDGFRA exons 12 and 18 mutations, respectively. The remaining 58(16.2%) patients were wild type. C-kit exon 9 mutations were mainly observed in the small intestine, while PDGFRA exons 12 and 18 mutations were strongly associated with the gastric. C-kit and PDFGRA mutation frequencies were not correlated with either tumor sizes or the nuclear mitotic. Conclusions    The stomach and small intestinal were the primary locations of GIST. GISTs were most commonly seen in c-kit exon 11 mutation. The types of c-kit and PDGFRA mutations were associated with the sites of origin in GISTs.