Tracking longitudinal genetic changes of circulating tumor DNA (ctDNA) in advanced Lung adenocarcinoma treated with chemotherapy
Tracking longitudinal genetic changes of circulating tumor DNA (ctDNA) in advanced Lung adenocarcinoma treated with chemotherapy
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追踪化疗治疗的晚期肺腺癌中循环肿瘤 DNA (ctDNA) 的纵向遗传变化
DOI：
10.1186/s12967-019-2087-9
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发表时间：
2019-10-10
影响因子：
7.4
通讯作者：
Shi, Yuankai
中科院分区：
文献类型：
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作者：
Han, Xiaohong;Han, Ying;Shi, Yuankai
培美曲塞联合铂配合物可作为晚期非鳞状非小细胞肺癌（NSCLC）的一线治疗，但个体疗效和安全性存在差异。有必要更好地了解与铂反应相关的遗传变异。材料与方法采用基于华大Oseq-ctDNA面板的新一代测序（NGS）技术，对32例肺腺癌患者在铂类化疗期间的98份纵向血浆样本进行分析，并建立了生物信息学管道来检测点突变。结果化疗后突变负担减轻，反映了化疗敏感性，尤其是C>G和C>A取代的频率。此外，肿瘤细胞携带一组特定的体细胞突变，如egfr （L858R）、KRAS(p。G12C)与铂处理明显相关。此外，MAPK通路被发现在NSCLC和铂基应答中起关键作用。最后，我们发现吸烟者从含铂化疗中获益较少。综上所述，本工作描述了铂类药物治疗过程中ctDNA突变状态的动态变化，可能为晚期肺腺癌患者分层和精准治疗提供依据。
IntroductionPemetrexed combined with platinum complexes can be used as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC), however, the efficacy and safety is varying from individuals. There is a need to better understand the genetic variations associated with platinum response.Materials and MethodsWe performed next-generation sequencing (NGS) based on BGI Oseq-ctDNA panel to analyze 98 longitudinal plasma samples from 32 lung adenocarcinoma patients during platinum-based chemotherapy, and a bioinformatic pipeline was developed to detect point mutations.ResultsWe found that mutation burden was decreased after chemotherapy, which reflected chemotherapy sensitivity, especially the frequency of C>G and C>A substitutions. Moreover, neoplastic cells carrying a specific set of somatic mutations, such asEGFR(L858R),KRAS(p.G12C) were obviously correlated with platinum treatment. In addition, the MAPK pathway was found to have a pivotal role in NSCLC and platinum based response. Finally, we found that smokers benefit less from platinum-based chemotherapy.ConclusionsCollectively, this work described the dynamic changes of ctDNA mutation status during platinum-based treatment, which may contribute to advanced lung adenocarcinoma patients stratification and precision treatment.