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PMID: 22327624 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

KIF5B-RET fusions in lung adenocarcinoma.

Nature medicine ·Vol. 18 ·No. 3 ·2012-02-12 ·Pages 375-7

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 AJ, Okayama H, Haugen A, Skaug V, Chiku S, Yamanaka I, Arai Y, Watanabe S, Sekine I, Ogawa S, Harris CC, Tsuda H, Yoshida T, Yokota J, Shibata T

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.

MeSH Terms

Adenocarcinoma/genetics,pathology Adenocarcinoma of Lung Anaplastic Lymphoma Kinase Animals Cell Transformation, Neoplastic/drug effects ErbB Receptors/genetics Gene Expression Regulation, Neoplastic High-Throughput Nucleotide Sequencing Humans Japan Kinesins/genetics Lung Neoplasms/genetics,pathology Mice NIH 3T3 Cells Norway Oncogene Proteins, Fusion/genetics Piperidines/pharmacology Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-ret/antagonists & inhibitors,genetics Proto-Oncogene Proteins p21(ras) Quinazolines/pharmacology Receptor Protein-Tyrosine Kinases/genetics Receptor, ErbB-2/genetics United States ras Proteins/genetics

Chemicals

KIF5B protein, human KRAS protein, human Oncogene Proteins, Fusion Piperidines Proto-Oncogene Proteins Quinazolines ALK protein, human Alk protein, mouse Anaplastic Lymphoma Kinase EGFR protein, human ERBB2 protein, human ErbB Receptors Proto-Oncogene Proteins c-ret RET protein, human Receptor Protein-Tyrosine Kinases Receptor, ErbB-2 Kinesins Proto-Oncogene Proteins p21(ras) ras Proteins N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine

Authors & Affiliations

29 authors, click to expand affiliations / ORCID

Kohno Takashi

Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan. tkkohno@ncc.go.jp

Ichikawa Hitoshi

Totoki Yasushi

Yasuda Kazuki

Hiramoto Masaki

Nammo Takao

Sakamoto Hiromi

Tsuta Koji

Furuta Koh

Shimada Yoko

Iwakawa Reika

Ogiwara Hideaki

Oike Takahiro

Enari Masato

Schetter Aaron J

Okayama Hirokazu

Haugen Aage

Skaug Vidar

Chiku Suenori

Yamanaka Itaru

Arai Yasuhito

Watanabe Shun-Ichi

Sekine Ikuo

Ogawa Seishi

Harris Curtis C

Tsuda Hitoshi

Yoshida Teruhiko

Yokota Jun

Shibata Tatsuhiro

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Article Info

Journal

Nature medicine

Abbr.

Nat Med

ISSN

1546-170X

DOI

10.1038/nm.2644

tkkohno@ncc.go.jp

Published

2012-02-12

Epub

2012-00-12

Pages

375-7

Language

English

Region

United States

NLM ID

9502015

PMCID

PMC6430196

Subset

Grants

Intramural NIH HHS · Z01 BC005480-23 · United States

Corrections

CommentIn

PMID: 22371133

CommentIn

PMID: 22395697

External Links

PubMed source DOI: 10.1038/nm.2644 PMC Full Text View journal details

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KIF5B-RET fusions in lung adenocarcinoma.

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