GeneKor Medical S.A., Athens 15344, Greece.
Pulmonary Department, Oncology Unit, 'G. Papanikolaou' General Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Oncol Rep. 2017 Dec;38(6):3419-3429. doi: 10.3892/or.2017.6051. Epub 2017 Oct 23.
Non‑small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissues. Furthermore, the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel was used for fusion RNA transcript analysis. The mutation spectrum of the tumors was determined in a cohort of 502 patients with NSCLC using the aforementioned targeted gene panels. The panel used for tumor DNA analysis in this study exhibited high rates (100%) of sensitivity, specificity and reproducibility at a mutation allelic frequency of 3%. At least one DNA mutation was detected in 374 patients (74.5%) and an RNA fusion was identified in 16 patients, (3.2%). In total, alterations in a cancer-driver gene were identified (including point mutations, gene rearrangements and MET amplifications) in 77.6% of the tumors tested. Among the NSCLC patients, 23% presented a mutation in a gene associated with approved or emerging targeted therapy. More specifically, 13.5% (68/502) presented a mutation in a gene with approved targeted therapy (EGFR, ALK, ROS1) and 9.4% (47/502) had an alteration in a gene related to emerging targeted therapies (ERBB2, BRAF, MET and RET). Furthermore, 51.6% of the patients had a mutation in a gene that could be related to an off label therapy or indicative for access to a clinical trial. Thus, the targeted NGS panel used in this study is a reliable approach for tumor molecular profiling and can be applied in personalized treatment decision making for NSCLC patients.
非小细胞肺癌（NSCLC）是最常见的肺癌类型，也是一种具有广泛靶向治疗药物的肿瘤，这些药物已经上市或正在临床试验中。因此，使用下一代测序（NGS）技术对肿瘤进行分子特征分析已成为促进治疗决策和 NSCLC 患者临床管理的关键工具。本研究评估了基于 Ion AmpliSeq™ 技术的定制 23 基因多重扩增热点面板用于分析福尔马林固定石蜡包埋（FFPE）组织提取的肿瘤 DNA 的性能。此外，还使用 Ion AmpliSeq™ RNA 融合肺癌研究面板进行融合 RNA 转录分析。使用上述靶向基因面板，在 502 例 NSCLC 患者的肿瘤中确定了肿瘤的突变谱。本研究中用于肿瘤 DNA 分析的面板在突变等位基因频率为 3%时，具有 100%的灵敏度、特异性和可重复性。在 374 例患者（74.5%）中检测到至少一种 DNA 突变，在 16 例患者（3.2%）中检测到 RNA 融合。在所有检测的肿瘤中，确定了癌症驱动基因的改变（包括点突变、基因重排和 MET 扩增），占 77.6%。在 NSCLC 患者中，23%的患者存在与已批准或新兴靶向治疗相关的基因突变。更具体地说，13.5%（68/502）的患者存在已批准靶向治疗相关基因（EGFR、ALK、ROS1）的突变，9.4%（47/502）的患者存在与新兴靶向治疗相关基因（ERBB2、BRAF、MET 和 RET）的改变。此外，51.6%的患者存在可能与非标签治疗相关或提示有资格参加临床试验的基因改变。因此，本研究中使用的靶向 NGS 面板是一种可靠的肿瘤分子谱分析方法，可用于 NSCLC 患者的个体化治疗决策。
