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Updated: Aug 23, 2026

Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
Protein Kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs)
Anette Duensing1, Nora E Joseph, Fabiola Medeiros
1Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. aduensin@pitt.edu
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.
Insights
Protein kinase C theta (PKCtheta) is a novel diagnostic marker for gastrointestinal stromal tumors (GISTs). This finding aids in diagnosing GISTs, even those lacking KIT expression, and suggests PKCtheta as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastrointestinal stromal tumors (GISTs) are typically diagnosed by KIT expression.
- Oncogenic KIT or PDGFRA mutations drive GIST development and are targeted by imatinib therapy.
- Low KIT expression in PDGFRA-mutant GISTs can lead to misdiagnosis as other sarcomas.
Purpose of the Study:
- To identify novel diagnostic markers for GISTs.
- To investigate the role of protein kinase C theta (PKCtheta) in GIST diagnosis.
- To explore PKCtheta as a potential therapeutic target in GISTs.
Main Methods:
- Analysis of KIT expression in GIST samples.
- Assessment of PDGFRA mutations in GISTs.
- Evaluation of PKCtheta activation as a diagnostic marker.
Main Results:
- PKCtheta is identified as a diagnostic marker in GISTs.
- PKCtheta is activated in GISTs, including those with low KIT expression or PDGFRA mutations.
- PKCtheta shows potential as a diagnostic tool for challenging GIST cases.
Conclusions:
- PKCtheta serves as a reliable diagnostic marker for GISTs, irrespective of KIT expression levels or PDGFRA mutations.
- PKCtheta activation is a common feature across most GISTs.
- PKCtheta represents a promising novel therapeutic target for GIST treatment.
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