中国肺腺癌患者上皮生长因子受体基因突变的研究

目的:分析我国肺腺癌患者上皮生长因子受体(EGFR)基因突变的发生率和突变类型。方法:在上海、杭州和昆明等地收集61例肺腺癌及其正常肺组织,采用PCR扩增和基因测序方法对组织DNA中EGFR外显子19~21基因突变进行分析。结果:正常肺组织中EGFR基因均为野生型,肺腺癌组织中EGFR基因突变检测率为47.5%(29/61),其中外显子19和21突变分别占突变总数的55.2%(16/29)和44.8%(13/29),外显子20未检测到突变。外显子19突变发生在第746~752位密码子,均为碱基缺失突变,有6种不同类型。外显子21突变全部是第858位密码子碱基替换突变。EGFR基因突变与患者性别和年龄无显著相关性。但昆明和上海等地患者的基因突变存在明显差异。结论:EGFR基因突变是一种肿瘤特异性的体细胞遗传改变,突变发生率约占肺腺癌总数的一半,其中以外显子19和21突变为主。我国EGFR基因突变存在地域差异。

Epidermal growth factor receptor mutations in Chinese patients with adenocarcinoma of the lung

Objective:To analyze the incidence and profile of mutations in epidermal growth factor receptor(EGFR) in Chinese patients with adenocarcinoma of the lung.Methods:Sixty one cases of lung adenocarcinoma tissue were collected from Shanghai,Hangzhou,and Kunming.For each case the normal lung samples were also available.The tissue DNA was abstracted and the exons 19 to 21 in EGFR gene were subjected for PCR amplification and direct sequencing.Results:The exon 19 to 21 of EGFR gene was wildtype in all normal lung tissues detected.Mutations were found in 29 cases of 61 neoplastic samples,with the incidence of 47.5 %.Mutations were mainly detected in exon 19(16/29 cases,55.2%) and exon 21(13/29 cases,44.8 %).No mutation in exon 20 was found.There were 6 types of EGFR mutation in exon 19,resulting in the deletion of the codon 746 to 752.The mutation in exon 21 belonged to the single missense substitution in the codon 858.There was no statistically significant difference between the mutations with gender and age.However,a marked difference in the mutation profile was noticed among the patients from Kunming and Shanghai.Conclusion:The EGFR mutation is a tumor-specific somatic abnormality.Some half the Chinese lung adenocarcinomas harbor the EGFR mutations,especially in the exon 19 and 21.There is a regional difference for EGFR mutation in China.