Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions.

Lovly CM, Gupta A, Lipson D, Otto G, Brennan T, Chung CT, Borinstein SC, Ross JS, Stephens PJ, Miller VA, Coffin CM
Cancer Discov. 2014 4 (8): 889-95

PMID: 24875859 · PMCID: PMC4125481 · DOI:10.1158/2159-8290.CD-14-0377

UNLABELLED - 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.

©2014 American Association for Cancer Research.

MeSH Terms (15)

Anaplastic Lymphoma Kinase Biomarkers, Tumor Child Crizotinib Humans Inflammation Male Neoplasms, Muscle Tissue Oncogene Proteins, Fusion Protein-Tyrosine Kinases Proto-Oncogene Proteins Pyrazoles Pyridines Receptor, Platelet-Derived Growth Factor beta Receptor Protein-Tyrosine Kinases

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