非小细胞肺癌患者癌组织表皮生长因子受体基因18～21号外显子的碱基序列突变情况观察  

Observation on base sequence mutations of exons 18-21 of epidermal growth factor receptor gene in patients with non-small-cell lung cancer

作　　者：周建平[1,2] 徐德 王代文 程君[1] ZHOU Jianping1 , XU De, WANG Daiwen, CHENG Jun(1 Medical College of Panzhihua University, Panzhihua 617000, China)

机构地区：[1]攀枝花学院医学院,四川攀枝花617000 [2]攀枝花学院附属医院 [3]攀枝花市中心医院

出　　处：《山东医药》2018年第31期1-4,共4页Shandong Medical Journal

基　　金：国家自然科学基金青年基金资助项目(81301893);四川省教育厅科技计划资助项目(14ZB0412);攀枝花市科技计划资助项目(2014TX-10-1)

摘　　要：目的观察非小细胞肺癌(NSCLC)患者癌组织表皮生长因子受体(EGFR)基因18~21号外显子的碱基序列突变情况。方法采用直接测序法检测72例份癌组织、20例份正常肺组织EGFR基因18~21号外显子碱基序列,分析并比较EGFR基因突变情况,与NCBI的EGFR临床基因突变数据库(Clin Var)比对分析碱基突变类型,确定样本突变类型是否为病理性突变,是否对应特定的药物反应类型。分析EGFR基因突变与NSCLC患者临床病理特征之间的关系。结果 NSCLC癌组织、正常肺部组织EGFR基因18~21号外显子的碱基突变率分别为58.3%(42/72)、0,二者比较,P<0.05。72例患者EGFR基因18~21外显子序列中共发现60种碱基突变,突变类型包括点突变、缺失突变、插入突变和插入/缺失突变。外显子18突变率8.3%(6/72),其中点突变4例;外显子19突变率29.2%(21/72),其中点突变21例、插入/缺失突变13例、病理性突变4例;外显子20突变率37.5%(27/72),其中点突变9例、缺失突变2例、插入/缺失突变1例、病理性突变1例;外显子21突变率4.2%(3/72),其中点突变1例、插入突变1例、病理性突变1例。与Clin Var比对后发现6种癌症病理相关碱基突变。其中良性变异1种(c.2361G>A),突变率31.9%(23/72);靶向药物敏感型突变1种(c.2830T>G),突变率2.8%(2/72);其它致癌相关突变4种。癌症病理相关突变率为12.5%(9/72),其中靶向药物敏感型突变的总体突变率为2.8%(2/72),其在EGFR突变样本中的比例为4.8%(2/42),外显子21突变c.2573T>G突变可导致EGFR蛋白Leu858Arg突变,是EGFR靶向药物治疗敏感型突变。结论 NSCLC癌组织EGFR基因18~21号外显子突变率较高,主要突变类型为点突变、缺失突变、插入突变和插入/缺失突变等。19号外显子基因突变情况最多,20号外显子突变类型最复杂。6种癌症病理相关突变中仅21号外显子中发现1种靶向药物敏感型突变。Objective To study the base sequence mutations in exons 18-21 of epidermal growth factor receptor（EGFR） gene in the cancer tissues of patients with non-small-cell lung cancer（NSCLC）. Methods The specimens of cancer tissues from 72 NSCLC patients were preserved during the operation. Another 20 specimens of normal lung tissues were collected as the controls. The sequences of EGFR exons 18-21 in the cancer tissues and normal lung tissues were detected by direct sequencing. The EGFR mutations were analyzed. We compared the type of base mutation with NCBI＇s EGFR clinical gene mutation database（Clin Var） to determine whether the sample mutation type was a pathological mutation and whether it corresponded to a specific drug response type. In addition,we analyzed the relationship between EGFR gene mutations and clinicopathological features of patients with NSCLC. Results The mutation rates of EGFR exons 18-21 in the NSCLC cancer tissues and normal tissues were 58. 3%（42/72） and 0,respectively,with significant difference（P〈0. 05）. Mutations were found in all 4 exons. Sixty specific mutations were found in the detected exons of EGFR. The mutation types included point mutation,deletion mutation,insertion mutation,and insertion/deletion mutation. The mutation rates of exons 18-21 were 8. 3%（6/72）,29. 2%（21/72）,37. 5%（27/72）,and 4. 2%（3/72）,respectively. Each exon had specific mutation types. There were 4,21,9 and 1 point mutations in exons 18-21,respectively. Other specific mutations included 13 insertion/deletion mutations in exon 19,2 deletion and 1 insertion/deletion mutations in exon 20,and 1 insertion mutation in exon 21. There were 6 cancer-associated mutations in this study,including 1 benign variation（c. 2361 G A） with mutation rate of 31. 9%（23/72）,1 drug-sensitive mutation（c. 2830 T G） with mutation rate of 2. 8%（2/72）,and 4 carcinogenic mutations. The overall rate of cancer-associated mutations was 12. 5%（9/72）. The targeted drug-sensitive mutations got a

关 键 词：肺肿瘤 非小细胞肺癌 表皮生长因子受体 外显子 基因突变 

分 类 号：R734.2[医药卫生—肿瘤]