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Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor

Authors

  • Zhigui Ma,

    1. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • D. Ashley Hill,

    1. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Margaret H. Collins,

    1. Department of Pathology, University of Cincinnati, Children's Hospital Medical Center, Cincinnati, Ohio
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  • Stephan W. Morris,

    Corresponding author
    1. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    3. Department of Pediatrics, University of Tennessee College of Medicine, Memphis, Tennessee
    • St. Jude Children's Research Hospital, Department of Pathology, Room 4026, Thomas Tower, 332 N. Lauderdale St., Memphis, TN 38105-2794
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  • Janos Sumegi,

    1. Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska
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  • Ming Zhou,

    1. Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska
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  • Craig Zuppan,

    1. Department of Pathology, Loma Linda University Medical Center, Loma Linda, California
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  • Julia A. Bridge

    1. Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska
    2. Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska
    3. Department of Orthopaedic Surgery, University of Nebraska Medical Center, Omaha, Nebraska
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Abstract

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal proliferation of transformed myofibroblasts, with a prominent inflammatory cell component, that can mimic other spindle cell processes such as nodular fasciitis, desmoid tumor, and gastrointestinal stromal tumor. Genetic analyses have recently demonstrated rearrangements of anaplastic lymphoma kinase (ALK), located at 2p23, in a subset of IMTs. Molecular characterizations have identified ALK fusions involving tropomyosin-3 and -4 (TPM-3 and -4), the clathrin heavy chain (CLTC), and the cysteinyl-tRNA synthetase (CARS) genes as fusion partners. Here we describe two IMTs with a novel ALK fusion that involves the Ran-binding protein 2 (RANBP2) gene at 2q13, which normally encodes a large (358-kDa) nucleopore protein localized at the cytoplasmic side of the nuclear pore complex. The N-terminal 867 residues of RANBP2 are fused to the cytoplasmic segment of ALK in the 1,430–amino acid RANBP2-ALK chimeric protein. Myofibroblasts that express RANBP2-ALK exhibit nuclear membrane-associated ALK staining that is unique compared to the subcellular localization observed with other ALK fusions in IMT, presumably attributable to heteroassociation of the fusion with normal RANBP2 at the nuclear pore. These findings expand the spectrum of ALK abnormalities observed in IMT and further confirm the clonal, neoplastic nature of these lesions. © 2003 Wiley-Liss, Inc.

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