基于二代测序技术探究食管鳞癌分子生物学特征及临床意义  

Exploring molecular characteristics of esophageal squamous cell carcinoma based on next-generation sequencing

作　　者：冯阿磊[1] 董青 逄娇慧 殷嘉妮 李强[1] 韩俊庆[1] 杨哲[1] FENG Alei;DONG Qing;PANG Jiaohui;YIN Jiani;LI Qiang;HAN Junqing;YANG Zhe(Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong University,Jinan 250021,Shandong, China;Nanjing Geneseeq Techonlogy Inc.,Nanjing 210032,Jiangsu,China)

机构地区：[1]山东大学附属省立医院肿瘤研究治疗中心,山东济南250021 [2]南京世和基因生物技术有限公司,江苏南京210032

出　　处：《山东大学学报（医学版）》2019年第7期80-85,91,共7页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81502508)

摘　　要：目的利用二代测序技术(NGS)对基因突变频率进行分析,探究食管鳞癌(ESCC)基因突变特征,寻找潜在的靶向治疗和免疫治疗靶点。方法随机收集49例山东省立医院确诊的ESCC患者的石蜡肿瘤组织样本,进行DNA提取,采用Illumina HiSeq4000测序平台对416个肿瘤相关基因进行捕获测序,测序结果进行生物信息学分析。结果发现TP53基因突变频率最高,并发现了多个ESCC潜在治疗靶点。EGFR 19del突变率和扩增率均为4.08%,未见EGFR L858R突变及KRAS突变;HER2和MET基因扩增发生率均为2.04%;BRCA1/2基因失活突变率约为8.06%;另外,MSI阳性率约为4.76%。提示携带相关靶点突变的患者可能是靶向治疗或免疫治疗的潜在获益人群。结论通过高通量检测技术发现ESCC多个潜在治疗靶点,对患者临床治疗方案的制定有重要意义。Objective To explore the potential molecular targets and gene mutation characteristics in esophageal squamous cell carcinoma (ESCC) by using next-generation sequencing. Methods DNA was extracted from tissue samples collected from 49 ESCC patients.The 416 cancer-relevant genes were sequenced with Illumina HiSeq4000 platform. The sequencing data were then subjected to bioinformatics analysis. Results TP53 was identified as the most frequently mutated gene, and multiple potential therapeutic targets were revealed. The mutation rate and amplification rate of EGFR 19del mutations were both 4.08%, while no EGFR L858R mutation or KRAS mutation was detected. The amplification rate of HER2 and MET were both 2.04%. The inactivating mutation rate of BRCA1/2 was 8.06%. The positive rate of MSI was 4.76%, indicating that ESCC patients with related target gene variations would potentially benefit from targeted therapies or immunotherapies. Conclusion Multiple potential therapeutic targets in ESCC are identified using next-generation sequencing, which can significantly guide personalized ESCC treatment.

关 键 词：食管鳞癌 二代测序 基因变异 靶向治疗 

分 类 号：R574[医药卫生—消化系统]