Abstract 1214: RET fusion gene: translation to the therapy of lung adenocarcinoma.

Abstract

Abstract A considerable proportion of lung adenocarcinomas, the most common histological type of lung cancer that comprises 40% of the total cases, develops through activation of oncogenes, for example, somatic mutations in EGFR or KRAS or fusion of ALK, in a mutually exclusive manner. Tyrosine kinase inhibitors targeting the EGFR and ALK proteins are effective in the treatment of lung adenocarcinomas that carry EGFR mutations and ALK fusions, respectively. We performed whole-transcriptome sequencing (RNA sequencing) of 30 lung adenocarcinoma specimens from Japanese individuals to identify new chimeric fusion transcripts that could be targets for therapy. Then, we identified KIF5B (kinesin family 5B)-RET fusion gene, as another druggable oncogene that is present in 2% (6/319) of lung adenocarcinomas (Kohno et al., Nat Med, 2012). The KIF5B-RET fusion leads to aberrant activation of RET kinase and is considered to be a new driver mutation segregating from mutations or fusions in EGFR, KRAS, HER2 and ALK. The RET fusion has preferentially been detected in well or moderately differentiated tumors of never smokers. The RET fusion in lung adenocarcinoma was also identified by three other groups: Dr. Ju et al of Seoul National University, Dr. Takeuchi et al of Japanese Foundation for Cancer Research, and Dr. Lipson et al of Foundation Medicine, USA. A clinical trial to address the therapeutic efficacy of a RET tyrosine kinase inhibitor, vandetanib, will be started in 2013 by Dr. Koichi Gotoh (kgoto@east.ncc.go.jp) of National Cancer Center Hospital East, Japan. Citation Format: Takashi Kohno, Hitoshi Ichikawa, Koji Tsuta, Tatsuji Mizukami, Yoko Shimada, Mamoru Kato, Hiromi Sakamoto, Katsuya Tsuchihara, Shun-ichi Watanabe, Hiroshi Nokihara, Koichi Goto, Jun Yokota, Teruhiko Yoshida, Tatsuhiro Shibata. RET fusion gene: translation to the therapy of lung adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1214. doi:10.1158/1538-7445.AM2013-1214