CRUK Lung Cancer Centre of Excellence, UCL Cancer Institute, UCL, London, United Kingdom; Department of Cellular Pathology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
Department of Oncology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
Lung Cancer. 2021 Nov;161:55-59. doi: 10.1016/j.lungcan.2021.08.008. Epub 2021 Aug 25.
There is an increasing number of driver fusions in NSCLC which are amenable to targeted therapy. Panel testing for fusions is increasingly appropriate but can be costly and requires adequate good quality biopsy material. In light of the typical mutual exclusivity of driver events in NSCLC, the objective of this study was to trial a novel testing pathway, supported by industrial collaboration, in which only patients negative for driver mutations on DNA-NGS were submitted for fusion panel analysis.
Over 18 months, all patients from a single centre with non-squamous NSCLC were submitted for DNA-NGS, plus ALK and ROS1 immunohistochemistry +/- FISH. Those which were negative for a driver mutation were then recalled for RNA panel testing.
307 samples were referred for DNA-NGS mutation analysis, of which, 10% of cases were unsuitable for or failed DNA-NGS analysis. Driver mutations were detected in 61% (167/275) of all those successfully tested. Of those without a driver mutation and with some remaining tissue available, 28% had insufficient tissue/extracted RNA or failed RNA-NGS. Of those successfully tested, 24% (17/72) had a fusion gene detected involving either ALK, ROS, MET, RET, FGFR or EGFR. Overall, 66% (184/277) of patients had a driver event detected through the combination of DNA and RNA panels.
Sequential DNA and RNA based molecular profiling increased the efficacy of detecting fusion driven NSCLCs. Continued optimisation of tissue procurement, handling and the diagnostic pathways for gene fusion analysis is necessary to reduce analysis failure rates and improve detection rate for treatment with the next generation of small molecule inhibitors.
非小细胞肺癌（NSCLC）中越来越多的驱动融合可通过靶向治疗。融合面板检测越来越适用，但成本高，需要足够的高质量活检材料。鉴于 NSCLC 中驱动事件的典型互斥性，本研究的目的是尝试一种新的检测途径，该途径得到了工业合作的支持，只有在 DNA-NGS 检测到无驱动突变的患者才进行融合面板分析。
在 18 个月的时间里，从一家单一中心的非鳞状 NSCLC 患者中收集了所有患者的 DNA-NGS 检测结果，以及 ALK 和 ROS1 免疫组化检测和 FISH 检测。那些 DNA-NGS 检测结果无驱动突变的患者被召回进行 RNA 面板检测。
307 例样本进行了 DNA-NGS 突变分析，其中 10%的病例不适合或无法进行 DNA-NGS 分析。在所有成功检测的病例中，61%（167/275）检测到了驱动突变。在没有驱动突变且有一些剩余组织的病例中，28%的组织/提取 RNA 不足或 RNA-NGS 检测失败。在成功检测的病例中，24%（17/72）检测到了融合基因，涉及 ALK、ROS、MET、RET、FGFR 或 EGFR。总体而言，通过 DNA 和 RNA 组合面板检测，66%（184/277）的患者检测到了驱动事件。
基于 DNA 和 RNA 的分子谱序分析序贯检测提高了检测融合驱动 NSCLC 的效果。需要进一步优化组织采集、处理和基因融合分析的诊断途径，以降低分析失败率，提高下一代小分子抑制剂治疗的检测率。
