No abstract

Inflammatory myofibroblastic tumor (IMT) is a neoplasm which typically occurs in children. The genetic landscape of this tumor is incompletely understood and therapeutic options are limited. While 50% of IMTs harbor ALK rearrangements, no therapeutic targets have been identified in ALK negative tumors. We report for the first time that IMTs harbor other actionable targets, including ROS1 and PDGFRβ fusions. We detail the case of an 8 year old boy with treatment-refractory ALK negative IMT. Molecular tumor profiling revealed a ROS1 fusion, and he had a dramatic response to the ROS1 inhibitor, crizotinib. This case prompted assessment of a larger series of IMTs. Next generation sequencing revealed that 85% of cases evaluated harbored kinase fusions, involving ALK, ROS1, or PDGFRβ. Our study represents the most comprehensive genetic analysis of IMTs to date and also provides rationale for routine molecular profiling of these tumors to detect therapeutically actionable kinase fusions.