Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, Japan.
Brain Tumor Pathol. 2019 Jan;36(1):14-19. doi: 10.1007/s10014-018-0330-3. Epub 2018 Oct 22.
The proto-oncogene tyrosine-protein kinase ROS1 (ROS1) is a tyrosine kinase that is closely related to anaplastic lymphoma kinase receptor (ALK). We describe a novel KLC1-ROS1 fusion identified in a case of pediatric low-grade glioma. This was detected by RNA sequencing and confirmed by reverse-transcription PCR and fluorescent in situ hybridization. Immunohistochemical staining for ROS1 was positive in the tumor cytoplasm. In vitro analysis demonstrated the oncogenic activity of this fusion, which was suppressed by the ALK/ROS1 inhibitor, crizotinib. Our case and others suggest that various ROS1 fusions might be present in a subset of pediatric gliomas, which could be targeted for therapy.
原癌基因酪氨酸蛋白激酶 ROS1（ROS1）是一种与间变性淋巴瘤激酶受体（ALK）密切相关的酪氨酸激酶。我们描述了一种在儿童低度神经胶质瘤病例中发现的新型 KLC1-ROS1 融合。该融合通过 RNA 测序检测到，并通过逆转录 PCR 和荧光原位杂交得到确认。ROS1 的免疫组织化学染色在肿瘤细胞质中呈阳性。体外分析显示该融合具有致癌活性，可被 ALK/ROS1 抑制剂克唑替尼抑制。我们的病例和其他病例表明，各种 ROS1 融合可能存在于儿童神经胶质瘤的一个亚群中，这些融合可能成为治疗的靶点。
