KIF5B-RET fusions in Chinese patients with nonsmall cell lung cancer

Abstract

National Natural Science Foundation of China [81172101]; Key Project of the Science and Technology Commission of Shanghai Municipality [11JC1411301]BACKGROUND: It has been established that ret proto-oncogene (RET) fusions are oncogenic drivers in nonsmall cell lung cancer (NSCLC). The prevalence and clinicopathologic characteristics of RET fusions in Chinese patients with NSCLC remain unclear. The objective of the current study was to determine the prevalence and clinicopathologic characteristics of KIF5B-RET fusions (fusions of the RET and kinesin family member 5B [KIF5B] genes) in Chinese patients with NSCLC. METHODS: The authors screened for KIF5B-RET fusions in 392 patients with NSCLC using multiplex real-time polymerase chain reaction assay and validated all positive samples using direct sequencing. The relations between KIF5B-RET fusions and clinicopathologic characteristics were analyzed. RESULTS: In total, 6 patients (1.5%) were identified who harbored KIF5B-RET fusions. Of these, 4 had adenocarcinoma, 1 had a malignant neuroendocrine tumor, and 1 had squamous cell carcinoma. All patients who were positive for a KIF5B-RET fusion were never-smokers. There was no statistically significant difference in age, sex, smoking status, pathologic stage, or histologic type between patients with and without KIF5B-RET fusions. Patients without KIF5B-RET fusions had a better prognosis than those with KIF5B-RET fusions (median survival, 52.6 months vs 21.0 months; P = .06), with a hazard ratio of 2.398 (95% confidence interval, 0.982-5.856; P = .055) on multivariate analysis. Disease stage (hazard ratio, 2.879) and younger age (<65 years; hazard ratio, 1.485) were identified as independent prognostic factors for better survival. CONCLUSIONS: KIF5B-RET fusions were quite rare, with a prevalence of approximately 1.5% in Chinese patients with NSCLC, and they were a little more common in patients with adenocarcinoma than in those with squamous carcinoma (1.73% vs 0.84%). In addition, KIF5B-RET fusions also existed in patients with low-grade malignant neuroendocrine tumors. Cancer 2013. (c) 2013 American Cancer Society