Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy.
Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy.
J Clin Pathol. 2018 Sep;71(9):767-773. doi: 10.1136/jclinpath-2018-205032. Epub 2018 Mar 13.
Molecular profiling of advanced non-small cell lung cancers (NSCLC) is essential to identify patients who may benefit from targeted treatments. In the last years, the number of potentially actionable molecular alterations has rapidly increased. Next-generation sequencing allows for the analysis of multiple genes simultaneously.
To evaluate the feasibility and the throughput of next-generation sequencing in clinical molecular diagnostics of advanced NSCLC.
A single-institution cohort of 535 non-squamous NSCLC was profiled using a next-generation sequencing panel targeting 22 actionable and cancer-related genes.
441 non-squamous NSCLC (82.4%) harboured at least one gene alteration, including 340 cases (63.6%) with clinically relevant molecular aberrations. Mutations have been detected in all but one gene () of the panel. Recurrent alterations were observed in , , , and genes, whereas the remaining genes were mutated in <5% of the cases. Concurrent mutations were detected in 183 tumours (34.2%), mostly impairing or EGFR in association with alterations.
The study highlights the feasibility of targeted next-generation sequencing in clinical setting. The majority of NSCLC harboured mutations in clinically relevant genes, thus identifying patients who might benefit from different targeted therapies.
对晚期非小细胞肺癌（NSCLC）进行分子谱分析对于确定可能受益于靶向治疗的患者至关重要。近年来，潜在的可靶向分子改变数量迅速增加。下一代测序可以同时分析多个基因。
评估下一代测序在晚期 NSCLC 临床分子诊断中的可行性和通量。
对 535 例非鳞状 NSCLC 进行了单中心队列研究，使用靶向 22 个可靶向和癌症相关基因的下一代测序面板进行分析。
441 例非鳞状 NSCLC（82.4%）至少存在一个基因改变，其中 340 例（63.6%）具有临床相关的分子异常。该面板中的所有基因均检测到突变，除一个基因（）外。在 、 、 、 和 基因中观察到复发性改变，而其余基因的突变在<5%的病例中。在 183 个肿瘤中检测到了同时存在的突变（34.2%），主要是与 改变相关的 或 EGFR 的功能缺失性突变。
该研究强调了靶向下一代测序在临床环境中的可行性。大多数 NSCLC 存在临床相关基因的突变，从而确定了可能受益于不同靶向治疗的患者。
