摘要
目的分析胃肠间质瘤(GIST)中c-kit、血小板源性生长因子受体A(PDGFRA)基因突变类型、特点及其与GIST临床病理学特征的关系。方法收集288例GIST患者的临床病理资料和肿瘤组织标本,应用聚合酶链式反应扩增-直接测序法检测c-kit(外显子9、11、13、17)与PDGFRA基因(外显子12、18)的突变状态,分析其突变类型、突变位点与临床病理学特征的关系。结果288例GIST患者中,原发性突变型244例(84.72%),继发性耐药突变型10例(3.47%),野生型34例(11.81%)。244例原发性突变型GIST患者中,c-kit基因突变231例(外显子9、11、13、17突变分别为25、189、7、10例),PDGFRA基因突变13例(外显子12、18突变分别为3、10例)。189例c-kit基因外显子11突变中,缺失突变111例(58.73%)、点突变65例(34.39%)、重复突变3例(1.59%)、插入突变4例(2.12%)、混合突变6例(3.17%);外显子11突变热点区域为557~560位密码子。突变位点与肿瘤原发部位、肿瘤大小、核分裂象计数有关(P<0.05);突变类型与患者年龄、肿瘤原发部位、肿瘤大小、核分裂像计数、改良美国国立卫生研究院(NIH)危险分级有关(P<0.05)。Logistic回归分析显示,大于60岁、缺失突变、c-kit外显子11突变的GIST患者,其改良NIH危险分级风险分别增高2.060(95%CI为1.066~3.980)、3.264(95%CI为1.628~6.545)、3.819(95%CI为1.585~9.205)倍。结论GIST中c-kit和PDGFRA基因突变率高且突变类型位点多样,与GIST患者临床病理及预后密切相关,可为GIST全程化管理提供参考。
Objective To analyze the types and characteristics of c-kit and platelet derived growth factor receptor A(PDGFRA)gene mutations in gastrointestinal stromal tumors(GIST)and their relationships with clinicopathological characteristics of GIST.Methods The clinicopathological data and tumor tissue specimens of 288 patients with GIST were collected,and the polymerase chain reaction amplification-direct sequencing method was used to detect the mutation status of c-kit(exons 9,11,13,17)and PDGFRA gene(exons 12,18),and the relationships between mutation types,sites and clinicopathological characteristics were analyzed.Results Among the 288 GIST cases,244 cases were primary mutations type(84.72%),10 cases were secondary drug-resistant mutations type(3.47%),and 34 cases were wild-type(11.81%).Among the 244 patients with primary mutant GIST,there were 231(94.67%)mutations in the c-kit gene,and the mutations in exons 9,11,13,and 17 were 25,189,7,and 10 cases,respectively.There were 13 cases with PDGFRA gene mutation,of which exon 12 and 18 mutations were 3 and 10 cases,respectively.Among 189 cases with c-kit gene exon 11 mutations,111 cases(58.73%)were deletion mutations,65 cases(34.39%)were point mutations,3 cases were repeated mutations(1.59%),4 cases were insertion mutations(2.12%),and 6 cases were mixed mutations(3.17%).The hot spot of exon 11 mutation was codons 557 to 560.The mutation site was related to the primary tumor site,tumor size and mitotic count(P<0.05).The type of mutation was related to the patient′s age,primary site of tumor,tumor size,mitotic count and modified National Institutes of Health(NIH)risk classification(P<0.05).Logistic regression analysis showed that GIST patients aged more than 60 years old,with deletion mutations and c-kit exon 11 mutations had an increased risk of modified NIH risk classification by 2.060(95%CI was 1.066 to 3.980),3.264(95%CI was 1.628 to 6.545)and 3.819(95%CI was 1.585 to 9.205)times.Conclusion The c-kit and PDGFRA genes in GIST have a high mutation rate and diverse muta
作者
石磊
陈平
王昊
赵伟
符德元
SHI Lei;CHEN Ping;WANG Hao;ZHAO Wei;FU Deyuan(Department of Gastrointestinal Surgery,Subei People′s Hospital in Jiangsu Province,Clinical Medical College of Yangzhou University,Yangzhou,Jiangsu,225001;Department of Thyroid and Breast Surgery,Subei People′s Hospital in Jiangsu Province,Clinical Medical College of Yangzhou University,Yangzhou,Jiangsu,225001)
出处
《实用临床医药杂志》
CAS
2021年第13期45-52,共8页
Journal of Clinical Medicine in Practice
基金
国家自然科学基金面上项目(82072909)
江苏省扬州市科技计划项目(YZ2018092)。
