Article

RANBP2 and CLTC are involved in ALK rearrangements in inflammatory myofibroblastic tumors

Department of Pathology, Johns Hopkins University, Park SB-202, 600 N. Wolfe Street, Baltimore MD 21287, USA.
Cancer genetics and cytogenetics (Impact Factor: 1.93). 08/2007; 176(2):107-14. DOI: 10.1016/j.cancergencyto.2007.04.004
Source: PubMed

ABSTRACT Inflammatory myofibroblastic tumors (IMTs) are rare soft tissue tumors occurring primarily in children and young adults. ALK gene rearrangements have been identified in this neoplasm, with fusion of the ALK gene at 2p23 to a number of different partner genes. Metaphase cytogenetic analyses of these tumors have been relatively few, however, and may help to identify additional variant partners. We report on an IMT from a 2-year-old boy with a karyotype of 45,XY,der(2)inv(2)(p23q12)del(2)(p11.1p11.2),-22. FISH showed ALK-RANBP2 fusion in this tumor. The breakpoint was cloned and the fusion was confirmed, making this the third reported case of IMT with ALK-RANBP2 fusion. In addition, we identified the ALK fusion partner in a previously reported IMT with t(2;17)(p23;q23) as CLTC, a gene reported to be involved in four other IMTs, and showed that the breakpoint involved a novel ALK-CLTC fusion. FISH evaluation of nine other IMTs identified CLTC as the fusion partner in one additional case, but RANBP2 was not involved in the remaining eight IMTs, suggesting that the variant partners involved in ALK rearrangements in IMTs are diverse.

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    • "The RANBP2 gene encodes a 358-kd nuclear pore protein [6], thus IMTs with RANBP2-ALK (IMT-RA) rearrangement display a unique nuclear membrane staining pattern. Most importantly, IMT-RA is possibly associated with a poor prognosis; however, this relation remains inconclusive, as fewer than 10 cases of IMTs with genetically confirmed RANBP2-ALK fusion have been reported to date [5,7-11]. Herein, we present 2 new cases of IMT-RA with follow-up information. "
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    ABSTRACT: Inflammatory myofibroblastic tumors (IMTs) are categorized as intermediate biologic neoplasms, whereas IMTs with genetic features of ran-binding protein 2 (RANBP2) and anaplastic lymphoma kinase (ALK) rearrangement (IMT-RAs) are possibly related to a more aggressive clinical course. However, fewer than 10 cases of IMT-RA have been reported to date. Herein, we present 2 new cases of IMT-RA in which both tumors recurred quickly after primary surgery; one patient died 3 months later from the disease, and the other patient has been living with the disease for 12 months. IMT-RAs are characterized by noncohesive epithelioid and rounded tumoral cell morphology, commonly derived from pelvic and peritoneal cavities, and frequently show larger tumor sizes. The relation between the clinicopathologic features and poor prognosis of IMT-RA is discussed. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3314123381007714
    Diagnostic Pathology 09/2013; 8(1):147. DOI:10.1186/1746-1596-8-147 · 2.41 Impact Factor
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    • "And the TGFR are potentially amenable to therapies for treatment of human breast disease[37]. In the Huntington's disease, parkingson's disease, oxidative phosphorylation, and alzheimer's disease pathways, CLTC is involved in inflammatory myofibroblastic tumors [38] and lower expression of MAPT is associated with HER2 overexpression [39]. "
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    BMC Medical Genomics 01/2013; 6(1). DOI:10.1186/1755-8794-6-S1-S6 · 3.91 Impact Factor
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