Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden.
Histopathology. 2019 Jun;74(7):1098-1102. doi: 10.1111/his.13839. Epub 2019 Apr 24.
Inflammatory myofibroblastic tumour (IMT) is a soft tissue tumour primarily affecting children and young adults. Approximately 50% of IMTs have gene fusions involving the receptor tyrosine kinase (RTK)-encoding ALK gene, providing a molecular rationale for treating IMT patients with unresectable tumours with tyrosine kinase inhibitors (TKI). However, a subset of IMT instead displays fusions affecting other RTKencoding genes, so far including NTRK3, PDGFRB and ROS1. Also, IMTs with variant RTK fusions may respond well to TKI treatment, but can be dif?cult to identify as they are negative for ALK staining at immunohistochemistry, the standard method for detection of ALK rearrangements.
We used RNA-sequencing to search for alternate fusion events in an ALK-negative IMT.
We found a novel fusion gene - FN1-IGF1R. The FN1 gene, encoding ?bronectin, is thought to provide a strong promoter activity for the kinase domain of the RTK insulin-like growth factor 1 receptor, a mechanism similar to previously described RTK fusions in IMT.
炎性肌纤维母细胞瘤（IMT）是一种主要影响儿童和青年的软组织肿瘤。大约 50%的 IMT 存在涉及受体酪氨酸激酶（RTK）编码 ALK 基因的基因融合，为治疗不可切除肿瘤的 IMT 患者提供了使用酪氨酸激酶抑制剂（TKI）的分子原理。然而，亚组的 IMT 反而显示出影响其他 RTK 编码基因的融合，迄今为止包括 NTRK3、PDGFRB 和 ROS1。此外，具有变异 RTK 融合的 IMT 可能对 TKI 治疗反应良好，但由于它们在免疫组织化学（检测 ALK 重排的标准方法）中为 ALK 染色阴性，因此可能难以识别。
我们使用 RNA 测序在 ALK 阴性的 IMT 中寻找其他融合事件。
我们发现了一种新的融合基因 - FN1-IGF1R。FN1 基因编码纤连蛋白，被认为可为胰岛素样生长因子 1 受体的 RTK 激酶结构域提供强大的启动子活性，这种机制类似于 IMT 中先前描述的 RTK 融合。
