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

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.