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Preliminary Communication

Expression of IGF-1 receptor in KIT/PDGF receptor-α wild-type gastrointestinal stromal tumors with succinate dehydrogenase complex dysfunction

    Margherita Nannini

    * Author for correspondence

    Department of Hematology & Oncological Sciences ‘L&A Seràgnoli’, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.

    ,
    Annalisa Astolfi

    ’Giorgio Prodi’ Cancer Research Center, University of Bologna, Bologna, Italy

    ,
    Paola Paterini

    ’Giorgio Prodi’ Cancer Research Center, University of Bologna, Bologna, Italy

    ,
    Milena Urbini

    ’Giorgio Prodi’ Cancer Research Center, University of Bologna, Bologna, Italy

    ,
    Donatella Santini

    Pathology Unit, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

    ,
    Fausto Catena

    U.O. Chirurgia d’ Urgenza, AOU Parma, Italy

    ,
    Valentina Indio

    Biocomputing Group, Department of Biology, University of Bologna, Bologna, Italy

    ,
    Rita Casadio

    Biocomputing Group, Department of Biology, University of Bologna, Bologna, Italy

    ,
    Antonio Daniele Pinna

    Transplant, General & Emergency Surgery Department, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

    ,
    Guido Biasco

    Department of Hematology & Oncological Sciences ‘L&A Seràgnoli’, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy

    ’Giorgio Prodi’ Cancer Research Center, University of Bologna, Bologna, Italy

    &
    Maria A Pantaleo

    Department of Hematology & Oncological Sciences ‘L&A Seràgnoli’, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy

    ’Giorgio Prodi’ Cancer Research Center, University of Bologna, Bologna, Italy

    Published Online:https://doi.org/10.2217/fon.12.170

    KIT/PDGF receptor-α (PDGFRA) wild-type (WT) gastrointestinal stromal tumors (GIST) are characterized by an overexpression of IGF-1 receptor (IGF1R) at the mRNA and protein level. More recently, germline and somatic mutations in succinate dehydrogenase (SDH) subunits A, B and C have been identified in KIT/PDGFRA WT sporadic GIST. Until now, the molecular basis of IGF1R overexpression in KIT/PDGFRA WT GIST has not been explained. In this brief report we investigate the status of the SDH complex at the genomic and protein level in relation to IGF1R expression at the mRNA and protein level in seven KIT/PDGFRA WT sporadic GIST patients. We found that IGF1R was upregulated in all patients harboring SDH mutations or displaying a SDH dysfunction, with respect to KIT/PDGFRA WT GIST without SDH mutations. Western blot analysis confirmed that all patients with an upregulation of IGF1R mRNA had detectable IGF1R protein expression. This report would suggest that IGF1R overexpression in KIT/PDGFRA WT GIST could be driven by the loss-of-function of the SDH mitochondrial complex.

    Papers of special note have been highlighted as: ▪▪ of considerable interest

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