胃肠道间质瘤c—kit及PDGFRA基因突变及其临床意义  

Status and clinical analysis of c-kit and PDGFRA mutations in the gastrointestinal stromal tumors

作　　者：杜春燕[1] 师英强[1] 周烨[1] 傅红[1] 赵广法[1] 

机构地区：[1]复旦大学附属肿瘤医院腹外科复旦大学上海医学院肿瘤学系,上海200032

出　　处：《中华胃肠外科杂志》2008年第4期371-375,共5页Chinese Journal of Gastrointestinal Surgery

摘　　要：目的探讨胃肠道间质瘤（GIST）中c-kit及PDGFRA基因突变的分子生物学特点及与临床参数间的关系。方法对141例GIST进行基因检测，用PCR扩增和基因测序的方法检测肿瘤c-kit基因第9、11、13和17外显子及PDGFRA基因第12和18外显子的序列，分析基因突变与GIST临床参数之间的关系。结果在141例GIST中共检测到c—kit基因突变108例（76．6％），其中11号外显子突变99例（70．2％，99／141）；9号外显子突变8例（5．7％，8／141）；13号外显子突变1例（0．7％，1／141）；未检测到17号外显子突变病例。97．0％为杂合性突变，3．0％为纯合性突变，11外显子突变方式以缺失突变最常见65．7％（65／99），其次为点突变（24．2％）和插入突变（串联重复）（10．1％）；突变位点多集中在5’端的经典热区，其次为3’端的框内串联重复。共检测到4例PDGFRA基因的突变．占无c—kit突变病例的12．1％（4／33），占CD117阴性GIST的40％（4／10），均为外显子18的突变。基因突变的发生率在GIST不同原发部位间差异有统计学意义（χ^2=7．229，P=0．027；χ^2=7．000，P=0．03），而与患者年龄、性别、肿瘤大小、核分裂、恶性潜能分级等均差异无统计学意义。结论GIST中存在c-kit及PDGFRA基因的突变；基因突变的发生率在不同原发部位间有差异。Objective To investigate the status of c-kit and PDGFRA mutations in the gastrointestinal stromal tumors （GIST） and explore the relationship between the mutations and the clinical features. Methods One hundred and forty-one cases were evaluated for the presence of c-kit and PDGFRA mutations. Exon 9,11,13, 17 of c-kit and exon 12, 18 of PDGFRA were analyzed by PCR amplification and direct sequencing. The relations of clinical features and mutational status were analyzed with statistical tools in this study. Results Among the 141 GISTs, c-kit mutations were identified in 76.6% （ 108/141 ） ： 70.2% （99/141） involving exon 11, 5.7% （8/141） involving exon 9, 0.7%（1/141） involving exon 13 and no mutation detected in exon 17. The gene mutations were mostly heterogeneous. The c-kit exon 11 mutational format included deletion （65.7%）, point mutation （24.2%） and insert duplications （10.1%）.The mutations clustered in the classic ＂hot spot＂ at the 5＇ end of the exon mostly heterogeneous and the second ＂hot spot＂ were internal tandem duplications（ITD） at the 3＇end of the exon. PDGFRA mutations were totally identified in 12.1%（4/33） of no-c-kit-mutation GISTs and 40%（4/10） of CD117-negative GISTs： all involving exon 18 with the mutations D842V. With the analysis between clinical features and mutation status, the significant difference of gene mutation rate in the different primary tumor organs（χ^2=7.229, P=0.027, χ^2=7.000, P=0.03） and no significant differences between the groups of age,gender,tumor size,mitotic rate, grade of malignant potential were found. Conclusion Most GISTs have the c-kit or PDGFRA gene mutation. There are significant difference between mutation and primary tumor organ.

关 键 词：胃肠道间质肿瘤 c—kit PDGFRA 基因突变 

分 类 号：R735[医药卫生—肿瘤] R734.2[医药卫生—临床医学]