Abstract 2299: Generation and Characterization of Inducible KIF5B-RET Mouse Model of Non-Small Cell Lung Cancer

Abstract The new precision oncology requires identification of driver oncogenes, validation of oncogene addiction, and development of oncogene-targeted drugs. Lung cancer is molecularly heterogeneous characterized by various genetic alterations, many of them occur at low frequencies. Recurrent RET fusion genes have been found in 1-2% of non-small cell lung cancer (NSCLC). Among them KIF5B-RET fusion is the most prevalent and occurs specifically in NSCLC. To develop an in vivo animal model for evaluation of KIF5B-RET fusion in lung adenocarcinoma, we generated transgenic mice containing a doxycycline (Dox)-inducible tetO-KIF5B-RET transgene. To express KIF5B-RET in lung type II epithelial cells, tetO-KIF5B-RET mice were crossed with CCSP-rtTA mice. CCSP-rtT/tetO-KIF5B-RET bitransgenic mice were induced with Dox and lung tissues were analyzed. KIF5B-RET mRNA and protein were detected in the lungs of Dox-induced CCSP-rtTA/tetO-KIF5B-RET bitransgenic mice. Histological examinations showed lung hyperproliferative lesions and tumors in Dox-induced CCSP-rtTA/tetO-KIF5B-RET bitransgenic mice. Thus, KIF5B-RET fusion is a driver oncogene sufficient to induce lung tumors in transgenic mice. Citation Format: Qingling Huang, Valentina E. Schneeberger, Noreen Luetteke, Chengliu Jin, Domenico Coppola, Jie Wu. Generation and characterization of inducible KIF5B-RET mouse model of non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2299. doi:10.1158/1538-7445.AM2015-2299