肺腺癌表皮生长因子受体基因突变及临床意义

Study on epidermal growth factor receptor genetic mutation in lung adenocarcinoma and its clinical significance

目的研究肺腺癌组织中表皮生长因子受体(EGFR)第18、19、21外显子基因突变频率和类型及其与临床特征的关系。方法收集90例肺腺癌患者肿瘤组织石蜡包埋标本,提取DNA,聚合酶链反应扩增EGFR外显子18、19、21序列,进行基因测序分析,结合患者临床资料分析EGFR基因突变频率和类型以及临床特点。结果 90例肺腺癌组织中未检测到18外显子突变;检测到19外显子突变11例(12.2%),其中碱基缺失突变10例,包括2 235核苷酸到2 249核苷酸缺失3例,2 240核苷酸到2 248核苷酸缺失1例,2 240核苷酸到2 253核苷酸缺失2例,2 240核苷酸到2 257核苷酸缺失3例,1例同时检测到2 240核苷酸到2 248核苷酸和2 251核苷酸到2 262核苷酸2个片段碱基的缺失,另1例为P741L错义突变;21外显子突变18例(20.0%),表现为碱基的替换突变,其中14例为L858R,L858M、A722V、K875R、Q787Q各1例。不同性别、年龄、肿瘤直径、临床分期、分化程度及有无淋巴结转移者之间比较,EGFR基因19、21外显子突变率比较差异无统计学意义(P>0.05)。结论肺腺癌肿瘤组织中EGFR外显子突变热点集中在19、21外显子,不同外显子的突变频率和类型不同;EGFR基因突变与患者的性别、年龄、肿瘤直径、临床分期、分化程度及淋巴结转移等临床特征无相关性。

Objective To explore the epidermal growth factor receptor（EGFR） 18,19,21 exon mutation in lung adenocareinoma tissues and its correlation with clinical feature. Methods A total of 90 cases with lung adenocareinoma tumor tissue specimens of paraffin embedding were collected to extracting DNA,with PCR amplification EGFR exon 18,19,21 series, gene sequencing analysis, and the EGFR gene mutation types and clinical features were analyzed combined with clinical information. Results In the 90 cases of lung adenoearcinoma tissues, Exon 18 mutations could not be detected;Exon 19 mutations were detected in 11 cases （12.2%）, including deletion mutation in 10 cases, of which 2 235 -2 249 deletion in 3 cases, 2 240 -2 248 deletion in 1 case ,2 240 -2 253 deletion in 2 cases ,2 240 -2 257 deletion in 3 cases, 1 case was detected in 2 240 -2 248 and 2 251 -2 262 segments deletion, 1 case of point mutations for P741L missense mutation ;21 exon mutations in 18 cases（20% ） which showed the base substitution mutation,including 14 cases of L858R, 1 case of L858M, 1 case of A722V,1 case of K875R and 1 case of Q787Q. Compared with different gender,age,tumor size,clinical stage,differentiation degree and the presence of lymph node metastasis, the difference between 19 and 21 EGFR gene exon mutation rate was not significant （P 〉 0. 05 ）. Conclusion In lung adenocarcinoma tumor tissue, EGFR mutations hotspot focus on the 19,21 exons, the mutations of frequency and type are different in different exon. These mutations are lack of correlation in clinical features of the patients＇ age, gender, tumor size, stage, grade and nodal metastasis.