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Cancer Discov. 2014 Aug;4(8):889-95. doi: 10.1158/2159-8290.CD-14-0377. Epub 2014 May 29.

Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions.

Author information

1
Department of Medicine, Vanderbilt University, Nashville, Tennessee. christine.lovly@vanderbilt.edu.
2
Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
3
Foundation Medicine, Cambridge, Massachusetts.
4
Division of Pathology, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
5
Department of Pediatrics, Vanderbilt University, Nashville, Tennessee.
6
Foundation Medicine, Cambridge, Massachusetts. Albany Medical College, Albany, New York.
7
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee.

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.

Comment in

PMID:
24875859
PMCID:
PMC4125481
DOI:
10.1158/2159-8290.CD-14-0377
[Indexed for MEDLINE]
Free PMC Article
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