RET, ROS1 and ALK fusions in lung cancer.
Through an integrated molecular- and histopathology-based screening system, we performed a screening for fusions of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1, receptor tyrosine kinase (ROS1) in 1,529 lung cancers and identified 44 ALK-fusion-positive and 13 ROS1-fusion-positive adenocarcinomas, including for unidentified fusion partners for ROS1. In addition, we discovered previously unidentified kinase fusions that may be promising for molecular-targeted therapy, kinesin family member 5B (KIF5B)-ret proto-oncogene (RET) and coiled-coil domain containing 6 (CCDC6)-RET, in 14 adenocarcinomas. A multivariate analysis of 1,116 adenocarcinomas containing these 71 kinase-fusion-positive adenocarcinomas identified four independent factors that are indicators of poor prognosis: age ≥ 50 years, male sex, high pathological stage and negative kinase-fusion status.
Pathology Project for Molecular Targets, the Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. kentakeuchi-tky@umin.net
Kengo
K
Takeuchi
Manabu
M
Soda
Yuki
Y
Togashi
Ritsuro
R
Suzuki
Seiji
S
Sakata
Satoko
S
Hatano
Reimi
R
Asaka
Wakako
W
Hamanaka
Hironori
H
Ninomiya
Hirofumi
H
Uehara
Young
Y
Lim Choi
Yukitoshi
Y
Satoh
Sakae
S
Okumura
Ken
K
Nakagawa
Hiroyuki
H
Mano
Yuichi
Y
Ishikawa
D016475:3T3 Cells; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010880:Piperidines / Q000494:pharmacology; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011799:Quinazolines / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012737:Sex Factors
C088832:CCDC6 protein, human; D003598:Cytoskeletal Proteins; C000715470:MAS1 protein, human; D015514:Oncogene Proteins, Fusion; D010880:Piperidines; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; C452423:vandetanib