KIF5B-RET fusions in lung adenocarcinoma
Open accessAbstract
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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The incidence of uncommon EGFR mutations is comparable to rare targetable driver genes such as ROS1 and RET.
“The need for appropriate management of patients with these uncommon mutations is increasing because the incidence of uncommon EGFR mutations is comparable to rare targetable driver genes such as ROS1 and RET.12, 13, 14, 15”
From Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy (2016) · cites this paper as [13]
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- Authors
- Kohno, T., Ichikawa, H., Totoki, Y., Yasuda, K., Hiramoto, M., Nammo, T., Sakamoto, H., Tsuta, K., Furuta, K., Shimada, Y., Iwakawa, R., Ogiwara, H., Oike, T., Enari, M., Schetter, A. J., Okayama, H., Haugen, A., Skaug, V., Chiku, S., Yamanaka, I., Arai, Y., Watanabe, S.-I., Sekine, I., Ogawa, S., Harris, C. C., Tsuda, H., Yoshida, T., Yokota, J., & Shibata, T.
- Affiliations
- National Cancer Center Research Institute (JP)
- National Center for Global Health and Medicine (JP)
- National Cancer Center Hospital (JP)
- National Institutes of Health (US)
- National Institute of Occupational Health (NO)
- Mizuho (Japan) (JP)
- StaGen (Japan) (JP)
- The University of Tokyo (JP)
- Corresponding author
- Shibata, Tatsuhiro
- ORCID
- Kohno, Takashi
- Ichikawa, Hitoshi
- Totoki, Yasushi
- Yasuda, Kazuki
- Hiramoto, Masaki
- Nammo, Takao
- Furuta, Koh
- Ogiwara, Hideaki
- Oike, Takahiro
- Schetter, Aaron J
- Okayama, Hirokazu
- Haugen, Aage
- Skaug, Vidar
- Yamanaka, Itaru
- Arai, Yasuhito
- Watanabe, Shun-ichi
- Sekine, Ikuo
- Ogawa, Seishi
- Harris, Curtis C
- Tsuda, Hitoshi
- Yoshida, Teruhiko
- Yokota, Jun
- Shibata, Tatsuhiro
- Venue
- Nature Medicine
- Published
- 2012-02-12
- Volume
- 18
- Issue
- 3
- Pages
- 375-377
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6430196
- OpenAlex
- W1981083257
- Cited by
- 834
- References
- 19
- Citations by year
- 2026: 16 · 2025: 26 · 2024: 34 · 2023: 51 · 2022: 41 · 2021: 60 · 2020: 74 · 2019: 46 · 2018: 58 · 2017: 60 · 2016: 60 · 2015: 66 · 2014: 96 · 2013: 102 · 2012: 42
- FWCI
- 78.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Japan Society for the Promotion of Science (23591330, 24390288, 23249052)
- National Cancer Institute (Z01BC005480)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- KIF5B-RET fusion, RET receptor tyrosine kinase, lung adenocarcinoma, RET inhibitors, vandetanib, driver mutations, anchorage-independent growth, EGFR, KRAS, HER2, anaplastic lymphoma kinase
- MeSH terms
- Adenocarcinoma of Lung, Anaplastic Lymphoma Kinase, Adenocarcinoma, Animals, Cell Transformation, Neoplastic, Humans, Japan, Lung Neoplasms, Norway, Piperidines, Proto-Oncogene Proteins, Quinazolines, United States, Oncogene Proteins, Fusion, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins p21(ras), Kinesins, ras Proteins, Erb-b2 Receptor Tyrosine Kinases, Receptor Protein-Tyrosine Kinases, NIH 3T3 Cells, Proto-Oncogene Proteins c-ret, Mice, High-Throughput Nucleotide Sequencing, ErbB Receptors
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