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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Detection of c-kit mutational status in small-cell lung cancer in a Chinese cohort
Ying Cheng1, Hui Li1, Lixia Ma1
1Division of Thoracic Oncology, Jilin Province Cancer Hospital Changchun, China.
Background:
Overexpression of KIT (CD117), a tyrosine kinase receptor, and its natural ligand, stem cell factor, are found in small-cell lung cancer (SCLC). Somatic mutations of the proto-oncogene c-kit constitutively activate KIT expression in a ligand-independent way. To explore the clinical value of the c-kit mutation as a potential target for therapy with tyrosine kinase inhibitors, the c-kit mutational status and KIT expression in tumors from Chinese patients with SCLC were analyzed.
Methods:
Using 107 paraffin-embedded SCLC tumor specimens, c-kit exons 9, 11, 13, and 17 were analyzed for mutations by polymerase chain reaction and direct sequencing.
Results:
There were no activating mutations in exons 9, 11, 13, or 17. However, a point mutation in intron 16 (81240 G>A) was found in 11 out of the 107 samples (10.3%), of which the majority were limited-stage SCLC (10/11, 90.9%). Immunohistochemical staining of tumors harboring the c-kit point mutation using the anti-CD117 antibody showed that the mutation status was not associated with the expression of KIT.
Conclusion:
These findings indicate that the incidence and the types of c-kit mutations in SCLC tumors found in Chinese are different from those of the Caucasian population. Nevertheless, c-kit mutations are similarly rare in both groups, implying that they may not be suitable targets for c-kit-based tyrosine kinase inhibitors.
Insights
KIT mutations are rare in Chinese small-cell lung cancer (SCLC) patients, with a unique intron 16 point mutation observed. These findings suggest c-kit mutations are unlikely targets for tyrosine kinase inhibitors in SCLC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- KIT (CD117) and stem cell factor are overexpressed in small-cell lung cancer (SCLC).
- Somatic c-kit mutations can constitutively activate KIT, presenting a potential therapeutic target.
Purpose of the Study:
- To investigate the clinical value of c-kit mutations as therapeutic targets in SCLC.
- To analyze c-kit mutational status and KIT expression in Chinese SCLC patients.
Main Methods:
- Polymerase chain reaction and direct sequencing were used to analyze c-kit exons 9, 11, 13, and 17 in 107 SCLC tumor specimens.
- Immunohistochemical staining assessed KIT expression.
Main Results:
- No activating mutations were found in the analyzed exons.
- A point mutation in intron 16 (81240 G>A) was identified in 10.3% of samples, predominantly in limited-stage SCLC.
- The c-kit point mutation was not associated with KIT protein expression.
Conclusions:
- The incidence and types of c-kit mutations in Chinese SCLC differ from Caucasian populations.
- C-kit mutations are rare in SCLC, suggesting limited suitability as targets for c-kit-based tyrosine kinase inhibitors.
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