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Protein Kinase C (PKC) Expression and Constitutive Activation in Gastrointestinal Stromal Tumors (GISTs)

¹ Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts; ² Department of Medicine, Oregon Health & Science University, OHSU Cancer Institute and Portland VA Medical Center, Portland, Oregon; ³ OHSU Cancer Institute and Department of Pathology, Oregon Health & Science University, Portland, Oregon; and ⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts

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 (PKC) is a diagnostic marker in GISTs, including those that lack KIT expression and/or contain PDGFRA mutations. PKC is strongly activated in most GISTs and hence may serve, along with KIT/PDGFRA, as a novel therapeutic target.

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