Abstract
We identified in-frame fusion transcripts of KIF5B (the kinesin family 5B gene) and the RET oncogene, which are present in 1–2% of lung adenocarcinomas (LADCs) from people from Japan and the United States, using whole-transcriptome sequencing. The KIF5B-RET fusion leads to aberrant activation of RET kinase and is considered to be a new driver mutation of LADC because it segregates from mutations or fusions in EGFR, KRAS, HER2 and ALK, and a RET tyrosine kinase inhibitor, vandetanib, suppresses the fusion-induced anchorage-independent growth activity of NIH3T3 cells.
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Acknowledgements
This work was supported in part by the program for promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NiBio), Grants-in-Aid from the Ministry of Health, Labour and Welfare for the 3rd-term Comprehensive 10-year Strategy for Cancer Control, the National Cancer Center Research and Development Fund and the Norwegian Cancer Society. National Cancer Center Biobank is supported by the National Cancer Center Research and Development Fund, Japan. We thank T. Urushidate, S. Ohashi, S. Mitani, K. Yokozawa, S. Wakai, C. Otsubo and H. Isomura of the National Cancer Center and D. Suzuki and K. Nagase of the National Center for Global Health and Medicine for technical assistance. We also thank J.D. Minna and L. Girard of the University of Texas Southwestern Medical Center, K. Kumamoto of Saitama Medical University and A. Okamoto of Jikei University for RET fusion screening, N. Morii of the National Institute of Advanced Industrial Science and Technology (AIST) for thermodynamic characterization of the KIF5B protein and M. Maekawa of the GSP laboratory for rapid preparation of the FISH probes.
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RNA sequencing: H.I., K.Y., M.H., T.N. and H.S. Sequence data processing: Y.T., S.C. and I.Y. Molecular biological analyses: T.K., Y.S., R.I., H. Ogiwara, T.O., M.E., A.J.S., H. Okayama, A.H., Y.A. and S.O. Clinical and pathological analyses: K.T., K.F., V.S., S.W., I.S. and H.T. Manuscript writing: T.K., H.I. and T.S. Study design: T.K., H.I., C.C.H., T.Y., J.Y. and T.S.
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Supplementary Note, Supplementary Methods, Supplementary Tables 1–6 and Supplementary Figures 1–9 (PDF 3140 kb)
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Kohno, T., Ichikawa, H., Totoki, Y. et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med 18, 375–377 (2012). https://doi.org/10.1038/nm.2644
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DOI: https://doi.org/10.1038/nm.2644
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