PDF file - 137KB, Summary of genomic coordinates for the kinase fusions identified in this study. The sample number is depicted in the far left column. For tumor samples in which a kinase fusion was identified, the genomic coordinates for of each of the fusion genes is indicated. There were no other recurrent alterations. *The FN1-ALK fusion was detected with RNA sequencing. #Sufficient material was available to verify these kinase fusions with RNA sequencing.
ARTICLE ABSTRACT
Inflammatory myofibroblastic tumor (IMT) is a neoplasm that typically occurs in children. The genetic landscape of this tumor is incompletely understood and therapeutic options are limited. Although 50% of IMTs harbor anaplastic lymphoma kinase (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 a rationale for routine molecular profiling of these tumors to detect therapeutically actionable kinase fusions.Significance: Our study describes the most comprehensive genomics-based evaluation of IMT to date. Because there is no “standard-of-care” therapy for IMT, the identification of actionable genomic alterations, in addition to ALK, is expected to redefine management strategies for patients with this disease. Cancer Discov; 4(8); 889–95. ©2014 AACR.See related commentary by Le and Doebele, p. 870This article is highlighted in the In This Issue feature, p. 855
