Department of Medical Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, 16 Jiangsu Road, Qingdao, 266005, China.
BGI-Qingdao Institute, Qingdao SINO-GERMAN Ecopark, 2877 Tuanjie Road, Qingdao, 266555, China.
Sci Rep. 2017 Nov 6;7(1):14605. doi: 10.1038/s41598-017-14962-0.
Next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) assays have provided a new method of identifying tumor-driving genes in patients with advanced non-small cell lung carcinoma (NSCLC), especially in those whose cancer tissues are unavailable or in those that have acquired treatment resistance. Here, we describe a total of 119 patients with advanced EGFR-TKI-naive NSCLC and 15 EGFR-TKI-resistant patients to identify somatic SNVs, small indels, CNVs and gene fusions in 508 tumor-related genes. Somatic ctDNA mutations were detected in 82.8% (111/134) of patients in the total cohort. Of the 119 patients with advanced NSCLC, 27.7% (33/119) were suitable for treatment with National Comprehensive Cancer Network (NCCN) guideline-approved targeted drugs. Actionable genetic alterations included 25 EGFR mutations, 5 BRAF mutations, and 1 MET mutation, as well as 1 EML4-ALK gene fusion and 1 KIF5B-RET gene fusion. In 19.3% (23/119) of the patients, we also identified genomic alterations with that could be targeted by agents that are in clinical trials, such as mTOR inhibitors, PARP inhibitors, and CDK4/6 inhibitors. Additionally, the EGFR T790M mutation was found in 46.7% (7/15) of the patients with EGFR-TKI-resistant NSCLC, suggesting that the NGS-based ctDNA assay might be an optional method to monitor EGFR-TKI resistance and to discover mechanisms of drug resistance.
下一代测序（NGS）为检测晚期非小细胞肺癌（NSCLC）患者肿瘤驱动基因提供了新方法，尤其是在肿瘤组织不可用或已发生治疗耐药的患者中。在此，我们共检测了 119 例初治晚期 EGFR-TKI 敏感 NSCLC 患者和 15 例 EGFR-TKI 耐药患者，以鉴定 508 个肿瘤相关基因中的体细胞 SNVs、小片段插入缺失、CNVs 和基因融合。在总计 134 例患者中，82.8%（111/134）检测到了体细胞 ctDNA 突变。在 119 例晚期 NSCLC 患者中，27.7%（33/119）适合接受 NCCN 指南批准的靶向药物治疗。潜在可治疗的遗传改变包括 25 例 EGFR 突变、5 例 BRAF 突变、1 例 MET 突变，以及 1 例 EML4-ALK 基因融合和 1 例 KIF5B-RET 基因融合。在 19.3%（23/119）的患者中，我们还鉴定出了可能与处于临床试验中的药物相关的基因组改变，如 mTOR 抑制剂、PARP 抑制剂和 CDK4/6 抑制剂。此外，在 15 例 EGFR-TKI 耐药的 NSCLC 患者中发现了 46.7%（7/15）的 EGFR T790M 突变，这表明基于 NGS 的 ctDNA 检测可能是监测 EGFR-TKI 耐药和发现耐药机制的可选方法。
