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Updated: Aug 17, 2026
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
[c-kit and PDGFRA mutations in 60 cases of gastrointestinal stromal tumors (GISTs)]
Hui-ying He1, Yi-ning Xiang, Yan Li
1Department of Pathology, Peking University School of Basic Medical Scienes, Beijng 100083, China.
Objective:
To explore the status of activating mutations of c-kit and PDGFRA in GIST of Chinese patients.
Methods:
Sixty GISTs, confirmed by immunoreactivity of CD117, CD34, SMA, S-100 and Desmin, were evaluated for the presence of c-kit exons 9, 11, 13 and 17 mutations, and PDGFRA exons 12 and 18 mutations. The PCR products were sequenced directly for mutations, using DNA extracted from paraffin-embedded tissue.
Results:
53% of the tumors were located in the stomach, 22% in the small bowel, 8% in the colo rectum, 2% in the esophagus and 15% in the extragastrointestinal tract. Immunohistochemical demonstrations of c-kit (CD117) were seen in 90% cases. Overall, c-kit mutations were detected in 63.3% of patients as follows: 58.3% in exon 11, 3.3% in exon 9, 1.7% in exon 13 and none in exon 17. The types of c-kit exon 11 mutations were mostly heterogeneous and clustered in the classic "hot spot" at the 5' end of exon 11, 42.9% being point mutation and in-frame deletion at Codon 557-560. 14.3% of cases showed internal tandem duplications (ITD) at the 3' end of exon 11 in a region of a second hot spot for c-kit mutations. Interestingly, these cases were associated with female predominance, stomach location and occurrence in older patients. The present study failed to identify a significant association between c-kit mutation status and risk of aggressive behavior in GISTs. Exon 9 mutations consisted of ITP of six nucleotides encoding Ala-Tyr. A new point mutation of L641P was revealed in exon 13. PDGFRA mutations were found in 5% of all the 60 cases with none of the positive cases expressed detectable KIT protein. The type of mutation was the commonest point mutation of D842V of exon 18.
Conclusion:
Most KIT expressing GIST show c-kit mutations that are preferentially located within the classic hot spot of exon 11. A second hot spot -ITD at the 3' end of exon 11 seems to associate with a subgroup of gastric GISTs in older females. c-kit exons 9, 13 and 17 mutations are rare events in GIST of China. PDGFRA oncogenic mutations are more likely seen in KIT-negative GISTs arising in the peritoneal surface and have an unfavorable clinical course.
Insights
Activating mutations in KIT (CD117) are common in Chinese gastrointestinal stromal tumors (GISTs), primarily in exon 11. PDGFRA mutations are rare and associated with KIT-negative GISTs.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Context:
- Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract.
- Activating mutations in KIT (CD117) and PDGFRA proto-oncogenes are key drivers in GIST pathogenesis.
- Understanding mutation status is crucial for targeted therapy and predicting prognosis.
Purpose:
- To investigate the prevalence and spectrum of activating mutations in c-kit and PDGFRA genes in Chinese GIST patients.
- To correlate mutation status with clinicopathological features and tumor location.
Summary:
- This study analyzed 60 GISTs from Chinese patients for mutations in c-kit (exons 9, 11, 13, 17) and PDGFRA (exons 12, 18).
- KIT mutations were found in 63.3% of cases, predominantly in exon 11 (58.3%), with a secondary hot spot (ITD) in exon 11 associated with specific demographics.
- PDGFRA mutations (D842V in exon 18) were identified in 5% of cases, mainly in KIT-negative GISTs.
Impact:
- Findings highlight the predominance of c-kit exon 11 mutations in Chinese GISTs, informing diagnostic and therapeutic strategies.
- Identification of a potential subgroup of gastric GISTs with exon 11 ITD mutations in older females warrants further investigation.
- The study underscores the importance of analyzing both KIT and PDGFRA mutations for comprehensive GIST characterization.
