Journal Article

KIF5B-RET fusions in lung adenocarcinoma

Ogawa, Seishi, Harris, Curtis C, Totoki, Yasushi, Nammo, Takao, Sakamoto, Hiromi, Ogiwara, Hideaki, Haugen, Aage, Tsuta, Koji, Hiramoto, Masaki, Furuta, Koh, Enari, Masato, Watanabe, Shun-ichi, Yokota, Jun, Arai, Yasuhito, Kohno, Takashi, Iwakawa, Reika, Schetter, Aaron J, Shimada, Yoko, Skaug, Vidar, Yasuda, Kazuki, Okayama, Hirokazu, Yamanaka, Itaru, Tsuda, Hitoshi, Yoshida, Teruhiko, Chiku, Suenori, Oike, Takahiro, Shibata, Tatsuhiro, Ichikawa, Hitoshi, Sekine, Ikuo

2012

Overview

The authors report a new type of genetic alteration in lung adenocarcinoma. Fusions of KIF5B with RET kinase are found in 1–2% of lung cancer patients, segregate from other known alterations and can potentially be targeted using RET kinase inhibitors. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/68 / 692/699/67/1612 / Adenocarcinoma / Adenocarcinoma - genetics / Adenocarcinoma - pathology / Adenocarcinoma of Lung / Anaplastic Lymphoma Kinase / Animals / Biomedical and Life Sciences / Biomedicine / brief-communication / Cancer / Cancer Research / Cell Transformation, Neoplastic - drug effects / DNA sequencing / Enzyme inhibitors / ErbB Receptors - genetics / ErbB-2 protein / Gene Expression Regulation, Neoplastic / Gene mutations / Genetic aspects / Health aspects / High-Throughput Nucleotide Sequencing / Humans / Infectious Diseases / Japan / Kinases / Kinesin / Kinesins - genetics / Lung cancer / Lung Neoplasms - genetics / Lung Neoplasms - pathology / Metabolic Diseases / Mice / Molecular Medicine / Mutation / Neurosciences / NIH 3T3 Cells / Norway / Nucleotide sequencing / Oncogene Proteins, Fusion - genetics / Pathology / Piperidines - pharmacology / Protein-tyrosine kinase / Proteins / Proto-Oncogene Proteins - genetics / Proto-Oncogene Proteins c-ret - antagonists & inhibitors / Proto-Oncogene Proteins c-ret - genetics / Proto-Oncogene Proteins p21(ras) / Quinazolines - pharmacology / ras Proteins - genetics / Receptor Protein-Tyrosine Kinases - genetics / Receptor, ErbB-2 - genetics / Ret protein / Risk factors / Transcriptomes / Tyrosine / United States