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      标题:非小细胞肺癌药物靶向位点的相关基因突变研究
      作者:潘长芳,赵胜科,李洋,赵小凯    (上海中医药大学附属龙华医院检验科,上海 200126)
      卷次: 2018年29卷19期
      【摘要】 目的 研究非小细胞肺癌(NSCLC)靶向药物相关基因突变情况。方法 收集2016年9月至2017年3月经上海中医药大学附属龙华医院确诊的265例非小细胞肺癌患者的组织样本。提取福尔马林固定石蜡包埋肿瘤组织DNA样本,建立与 Illumina测序仪相匹配的文库,应用NextSeq 500测序仪进行测序,应用序列比对软件BWA,检测突变软件Freebayes进行与肺癌相关的ALK、BRAF、EGFR、HER2、KRAS、MET、NRAS、PIK3CA、RET、ROS1等基因的突变检测。结果 研究发现,265例非小细胞肺癌患者中,60岁以上患者人群与60岁以下患者人群基因突变率相比(58.62% vs 61.24%)差异无统计学意义(P>0.05),女性基因突变率为68.70%,明显高于男性的54.00%,差异有统计学意义(P<0.05);不同病理分型中肺腺癌基因突变率为66.67%,明显高于肺鳞癌的53.90%,差异有统计学意义(P<0.05);肺腺癌患者的EGFR基因突变率为48.64%,与肺鳞癌患者的46.75%比较差异无统计学意义(P>0.05);在突变类型中,肺腺癌患者的p.L858R突变率为30.63%,明显高于肺鳞癌患者的17.53%,肺鳞癌患者的19del突变率为21.43%,明显高于肺腺癌患者的11.71%,差异均有统计学意义(P<0.05);肺腺癌患者的PIK3CA位点突变率为4.93%,明显高于肺鳞癌患者的 1.30%,差异有统计学意义(P<0.05),而HER2、ALK、BRAF、KARS、MET、RET、ROS1、NRAS等基因位点突变率比较差异均无统计学意义(P>0.05)。结论 基因位点突变检测在非小细胞肺癌患者病理分型及指导靶向用药有一定的意义与价值。
      【关键词】 非小细胞肺癌;靶向药物;高通量测序;基因突变
      【中图分类号】 R734.2 【文献标识码】 A 【文章编号】 1003—6350(2018)19—2696—03
Mutation study of related genes in non-small cell lung cancer drug targeting sites. PAN Chang-fang, ZHAOSheng-ke, LI Yang, ZHAO Xiao-kai. Department of Clinical Laboratory, Longhua Hospital Affiliated to Shanghai Universityof Traditional Chinese Medicine, Shanghai 200126, CHINA
      【Abstract】 Objective To study the mutations of related genes of drug targeting sites in non-small cell lung can-cer (NSCLC). Methods A total of 265 tissue samples were collected from patients with non-small cell lung cancer di-agnosed by Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine during September 2016and March 2017. The DNA samples of FFPE tumor tissue were extracted to establish a library that matches the Illuminasequencer. DNA samples were sequenced by NextSeq 500 sequencer, and mutations in lung cancer-associated genes(ALK, BRAF, EGFR, HER2, KRAS, MET, NRAS, PIK3CA, RET, ROS1 and so on) were detected using sequence alignmentsoftware BWA and mutation detection software Freebayes. Results There was no statistically significant difference ingene mutation rate between the patients over 60 years old and those under the age of 60 (58.62% vs 61.24%, P<0.05) in265 patients with non-small cell lung cancer. The gene mutation rate of female (68.70%) was significantly higher thanthat of the male (54.00%), and the difference was statistically significant (P<0.05). The mutation rate of lung adenocarci-noma (66.67%) was significantly higher than that of lung squamous cell carcinoma (53.90%) in different pathologicaltypes, and the difference was statistically significant (P<0.05). The mutation rate of EGFR gene in lung adenocarcino-ma patients (48.64% ) was not statistically significant different from that of lung squamous cell carcinoma patients(46.75%), P>0.05. Among the mutation types, the p.L858R mutation rate in patients with lung adenocarcinoma (30.63%)was significantly higher than that of lung squamous cell carcinoma patients (17.53%), and the mutation rate of 19del inlung squamous cell carcinoma (21.43% ) was significantly higher than that in patients with the lung adenocarcinoma(11.71%), with statistically significant differences (P<0.05). The mutation rate of PIK3CA locus in patients with lung ad-enocarcinoma (4.93% ) was significantly higher than that in patients with lung squamous cell carcinoma (1.30% ), P<0.05. The mutation rates of HER2, ALK, BRAF, KARS, MET, RET, ROS1 and NRAS were not significantly different be-tween two groups, and all differences were not statistically significant (P>0.05). Conclusion The detection of gene locimutation shows certain significance and value in the pathological typing of non-small cell lung cancer patients andshows guidance in targeted drug usage.
      【Key words】 Non-small cell lung cancer (NSCLC); Targeted drug; High throughput sequencing; Gene mutation·论 著·doi:10.3969/j.issn.1003-6350.2018.19.009

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