Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjing, China.
Lung Cancer. 2019 Mar;129:92-94. doi: 10.1016/j.lungcan.2018.12.011. Epub 2018 Dec 19.
Non-small-cell lung cancer (NSCLC) has various driver mechanisms, including ROS1 rearrangement with different fusion patterns. There is a need to identify and evaluate new ROS1 fusions and the response to targeted therapy.
A targeted next-generation sequencing (NGS) panel was used to analyze DNA extracted from tumor tissue and blood samples from an NSCLC patient. Results were validated using Sanger sequencing.
We found a novel ROS1 rearrangement form, namely a WNK1-ROS1 fusion. The transmembrane and kinase domains of ROS1 remained intact in this fusion. No EGFR, MET, KRAS, ALK, ROS1 or other NSCLC driver mutations were detected in the patient. The patient achieved a partial response after treatment with crizotinib. When disease progressed, ROS1 G2032R mutation-a classical mechanism of crizotinib resistance-was detected in the DNA sample extracted from the patient's plasma sample.
We identified a novel WNK1-ROS1 fusion that was sensitive to crizotinib and developed an ROS1 G2032R mutation when the disease progressed. The WNK1-ROS1 rearrangement appeared to be a novel driver of the lung cancer.
非小细胞肺癌（NSCLC）具有多种驱动机制，包括不同融合模式的 ROS1 重排。需要识别和评估新的 ROS1 融合以及对靶向治疗的反应。
使用靶向下一代测序（NGS）面板分析来自 NSCLC 患者肿瘤组织和血液样本中的 DNA。使用 Sanger 测序验证结果。
我们发现了一种新的 ROS1 重排形式，即 WNK1-ROS1 融合。该融合保留了 ROS1 的跨膜和激酶结构域。在患者中未检测到 EGFR、MET、KRAS、ALK、ROS1 或其他 NSCLC 驱动突变。该患者在接受克唑替尼治疗后获得部分缓解。当疾病进展时，在从患者血浆样本中提取的 DNA 样本中检测到 ROS1 G2032R 突变——克唑替尼耐药的经典机制。
我们鉴定出一种对克唑替尼敏感的新型 WNK1-ROS1 融合，并在疾病进展时出现了 ROS1 G2032R 突变。WNK1-ROS1 重排似乎是肺癌的一种新驱动因素。
