浙江地区晚期非小细胞肺癌患者循环肿瘤DNA突变特征的检测

Detection of mutation characteristics of circulating tumor DNA in patients with advanced non-small cell lung cancer in Zhejiang area

目的初步探究浙江地区晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者循环肿瘤DNA(circulating tumor DNA,ctDNA)的突变特征并为患者提供临床靶向用药理论依据。方法采用高通量测序技术,对79例浙江籍贯的NSCLC患者的ctDNA样本进行基因靶向捕获深度测序,对测序结果进行回顾性统计分析。结果 EGFR基因的突变频率最高,达到56.5%,发现的高频突变还包括存在于TP53(33.3%)、KRAS(30.4%)、ERBB2(23.2%)、FGFR1(18.8%)、PTEN(15.9%)等基因的致病位点。EGFR突变更容易出现在女性、不吸烟、肺腺癌患者(P<0.05),KRAS突变更容易出现在年轻、吸烟患者(P<0.05),ERBB2突变容易出现在不吸烟的患者(P<0.05)。在44例(44/79,55.7%)中共发现了存在于8个基因的29个靶向用药位点突变,在22例(22/44,50.0%)中检测到同时存在多个用药位点的现象,9例以往接受过酪氨酸激酶抑制剂药物治疗的复发患者均检测到T790M突变。结论 NSCLC具有十分复杂的突变特征,基于ctDNA的高通量测序在一定程度上可以较全面反映肿瘤的分子特征,为患者提供更多的靶向用药指导。

Objective To investigate the mutation characteristics of circulating tumor DNA(ctDNA)in patients with advanced non-small cell lung cancer(NSCLC)in Zhejiang,and to provide theoretical basis for clinical targeted drug use.Methods High-throughput sequencing technology was used for targeted capture and deep sequencing of the ctDNA samples of 79 patients with NSCLC in Zhejiang,and the sequencing results were retrospectively analyzed.Results The mutation frequency of EGFR gene was the highest,reaching 56.5%.The high frequency mutations included sites on TP53(33.3%),KRAS(30.4%),ERBB2(23.2%),FGFR1(18.8%),PTEN(15.9%),etc.The EGFR mutations were more likely to occur in women,non-smokers,and patients with lung adenocarcinoma(P<0.05).The KRAS mutations were more likely to occur in young patients and smokers(P<0.05).The ERBB2 mutations were more likely to occur in non-smokers(P<0.05).In 44 cases(44/79,55.7%),29 targeted drug site mutations were found in 8 genes,and multiple drug sites were detected in 22 cases(22/44,50.0%).The T790M mutation was detected in 9 relapsed patients who had previously received tyrosine kinase inhibitor therapy.Conclusion NSCLC has very complex mutation characteristics.High-throughput sequencing based on ctDNA can reflect the molecular characteristics of tumors to a certain extent,and provide more targeted drug guidance for patients.