Protein Kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs).
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.
Duensing
Anette
A
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. aduensin@pitt.edu
Joseph
Nora E
NE
Medeiros
Fabiola
F
Smith
Felicity
F
Hornick
Jason L
JL
Heinrich
Michael C
MC
Corless
Christopher L
CL
Demetri
George D
GD
Fletcher
Christopher D M
CD
Fletcher
Jonathan A
JA
D004789:Enzyme Activation; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism*; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D016335:Zinc Fingers
D007527:Isoenzymes; D015513:Oncogene Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta