Detection of c‐kit mutational status in small‐cell lung cancer in a Chinese cohort

Abstract

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.

Mutation and expression of the C-KIT gene on population of Kazakhstan

“…The receptor can also be constitutively activated independently on the ligand by specific mutations of the C-KIT gene. Expression of C-KIT protein was detected in 79-88% of SCLC cell lines, and during the inactivation of C-KIT the tyrosine kinase inhibitor imatinib had an inhibitory effect on SCLC cell growth [15].…”

Small Cell Lung cancer: Molecular Oncology Approach

“…SCLC cells express cancKIT receptor and its ligand stem cell factor in 40-60% [15,35,36]. When binding to its ligand this receptor activate JAK-STAT, PI3K and MAP kinase pathways.…”