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  • Title: Protein Kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs).
    Author: Duensing A, Joseph NE, Medeiros F, Smith F, Hornick JL, Heinrich MC, Corless CL, Demetri GD, Fletcher CD, Fletcher JA.
    Journal: Cancer Res; 2004 Aug 01; 64(15):5127-31. PubMed ID: 15289315.
    Abstract:
    KIT expression is a key diagnostic feature of gastrointestinal stromal tumors (GISTs), and virtually all of the GISTs express oncogenic forms of the KIT or PDGFRA receptor tyrosine kinase proteins, which serve as therapeutic targets of imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). However, KIT expression can be low in PDGFRA-mutant GISTs, increasing the likelihood of misdiagnosis as other types of sarcoma. We report that the signaling intermediate protein kinase C theta (PKCtheta) is a diagnostic marker in GISTs, including those that lack KIT expression and/or contain PDGFRA mutations. PKCtheta is strongly activated in most GISTs and hence may serve, along with KIT/PDGFRA, as a novel therapeutic target.
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