KIF5B-RET fusions in lung adenocarcinoma.
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.
Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan. tkkohno@ncc.go.jp
Takashi
T
Kohno
Hitoshi
H
Ichikawa
Yasushi
Y
Totoki
Kazuki
K
Yasuda
Masaki
M
Hiramoto
Takao
T
Nammo
Hiromi
H
Sakamoto
Koji
K
Tsuta
Koh
K
Furuta
Yoko
Y
Shimada
Reika
R
Iwakawa
Hideaki
H
Ogiwara
Takahiro
T
Oike
Masato
M
Enari
Aaron J
AJ
Schetter
Hirokazu
H
Okayama
Aage
A
Haugen
Vidar
V
Skaug
Suenori
S
Chiku
Itaru
I
Yamanaka
Yasuhito
Y
Arai
Shun-Ichi
S
Watanabe
Ikuo
I
Sekine
Seishi
S
Ogawa
Curtis C
CC
Harris
Hitoshi
H
Tsuda
Teruhiko
T
Yoshida
Jun
J
Yokota
Tatsuhiro
T
Shibata
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007564:Japan; D016547:Kinesins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D041681:NIH 3T3 Cells; D009664:Norway; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010880:Piperidines / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D014481:United States; D018631:ras Proteins / Q000235:genetics
D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D016547:Kinesins; D015514:Oncogene Proteins, Fusion; D010880:Piperidines; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C488101:KIF5B protein, human; C117307:KRAS protein, human; C000626173:ALK protein, human; C000626174:Alk protein, mouse; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C099282:RET protein, human; C452423:vandetanib