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185例华南地区非小细胞肺癌EGFR基因突变分析

EGFR gene mutation analysis among 185 cases of NSCLC patients in south of China

摘要:

目的 探讨华南地区非小细胞肺癌(NSCLC)表皮生长因子受体(EGFR)基因突变特点及与临床特征的关系.方法 收集本院185例NSCLC肿瘤组织,分别提取DNA,采用荧光PCR法扩增EGFR基因第18、19、20、21号外显子,对扩增片段进行DNA正反向测序并分析.结果 185例NSCLC中,62例(33.5%)EGFR基因突变,其中18、19、20、21外显子突变分别为2例、41例、5例、14例;共见突变类型16种,热点突变类型为19外显子Del L747 →P752 (P753S)(构成比8.1%)、Del E746 → A750(构成比45.1%)和21外显子L858R(构成比22.6%);其中4例19外显子突变正、反向测序结果不一致.见20外显子2361G →A沉默突变(28.1%);女性突变率显著高于男性(46.2%vs24.3%,x2 =9.670,P=0.002).不吸烟者突变率高于吸烟者(41.4%vs17.1%,x2 =7.380,P=0.007).腺癌患者突变率高于鳞癌患者(38.3% vs 6.3%,x2=6.426,P=0.011).临床Ⅲ期患者突变率显著低于临床Ⅱ期、Ⅳ期患者(10.8% vs 53.8%,x2=8.026,P=0.003;10.8%vs41.3%,x2=9.518,P=0.002).同时,未发现EGFR基因突变率与年龄相关.结论 华南地区NSCLC患者EGFR基因突变以19、21外显子突变为主.突变率以女性、不吸烟、腺癌者较高.

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abstracts:

Objective To investigate the characteristics of EGFR gene mutations among NSCLC patients in south of China and analyze the correlation between mutations and clinical features.Methods Specimens of lung cancer tissues were collected from 185 NSCIC patients in our hospital.DNA was extracted from specimens.Exon 18,19,20 and 21 of EGFR gene were amplified by FQ-PCR to be bi-directional sequenced.Results EGFR gene mutations in 62 (33.5%) of 185 NSCLC patients was identified in carcinoma tissues,of which,2cases,41cases,5 cases and 14 cases respectively located at exon 18,exon 19,exon 20 and exon 21.The mutation of Del L747 → P752 (P753S) ( proportion 8.1% ),Del E746 → A750 ( proportion 45.1% ) at exon 19 and L858R ( proportion 22.6% ) at exon 21 were the predominant mutation in 16 kinds of mutations.Four cases of mutation at exon 19 got the different results in bi-directional sequencing.The silent mutation 2361G →A at exon 20 was observed (28.1% ).The mutation rate in women was significantly higher than men (46.2% vs 24.3%,x2 =9.670,P =0.002).Non-smokers had significantly higher mutation rate than smokers (41.4% vs 17.1%,x2 =7.380,P =0.007) ; Adenocarcinoma patients had significantly higher mutation rate than squamous cell carcinoma (38.3% vs 6.3%,x2 =6.426,P =0.011).Clinical stage Ⅲ patients had significantly lower mutation ratethan patients with stage Ⅱ or Ⅳ ( 10.8% vs 53.8%,x2 =8.026,P =0.003 ;10.8% vs 41.3%,x2 =9.518,P =0.002).No statistically significance correlation was found between the mutation ratio and age.Conclusions EGFR gene mutation has a close relationship with females,non-smokers and adenocarcinoma.Most mutations occur in exon 19 and 20 among patients in south of China.

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