Tyrosine kinase gene rearrangements in epithelial malignancies
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TLDR
The clinical outcomes with targeted therapies, aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET are examined.Abstract:
In this Review, the authors examine the aetiological, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, the clinical outcomes with targeted therapies, and strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours. Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as 'druggable' targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours.read more
Citations
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The emerging complexity of gene fusions in cancer
TL;DR: The spectrum of gene fusions in cancer and how the methods to identify them have evolved are described, and the conceptual implications of current, sequencing-based approaches for detection are discussed.
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The landscape and therapeutic relevance of cancer-associated transcript fusions.
Kosuke Yoshihara,Qianghu Wang,Wandaliz Torres-Garcia,Siyuan Zheng,Rahulsimham Vegesna,Hoon Kim,Roel G.W. Verhaak +6 more
TL;DR: The landscape of transcript fusions detected across a large number of tumor samples was described and revealed fusion events with clinical relevance that have not been previously recognized, support the concept of basket clinical trials and reveal an important role for tumorigenesis.
References
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Roberto Chiarle,Claudia Voena,Chiara Ambrogio,Roberto Piva,Roberto Piva,Giorgio Inghirami,Giorgio Inghirami +6 more
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Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies
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TL;DR: Applying a next-generation sequencing assay targeting 145 cancer-relevant genes in 40 colorectal cancer and 24 non–small cell lung cancer formalin-fixed paraffin-embedded tissue specimens identified at least one clinically relevant genomic alteration in 59% of the samples and revealed two gene fusions, C2orf44-ALK in a colorective cancer sample and KIF5B-RET in a lung adenocarcinoma.
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KIF5B-RET fusions in lung adenocarcinoma.
Takashi Kohno,Hitoshi Ichikawa,Yasushi Totoki,Kazuki Yasuda,Masaki Hiramoto,Takao Nammo,Hiromi Sakamoto,Koji Tsuta,Koh Furuta,Yoko Shimada,Reika Iwakawa,Hideaki Ogiwara,Takahiro Oike,Masato Enari,Aaron J. Schetter,Hirokazu Okayama,Aage Haugen,Vidar Skaug,Suenori Chiku,Itaru Yamanaka,Yasuhito Arai,Shun-ichi Watanabe,Ikuo Sekine,Seishi Ogawa,Curtis C. Harris,Hitoshi Tsuda,Teruhiko Yoshida,Jun Yokota,Tatsuhiro Shibata +28 more
TL;DR: In-frame fusion transcripts of KIF5B (the kinesin family 5B gene) and the RET oncogene are identified and a RET tyrosine kinase inhibitor, vandetanib, suppresses the fusion-induced anchorage-independent growth activity of NIH3T3 cells.
Journal ArticleDOI
Activation of a novel human transforming gene, ret, by DNA rearrangement
TL;DR: A novel transforming gene was detected by transfection of NIH 3T3 cells with human lymphoma DNA and appeared to be activated by recombination between two unlinked human DNA segments, possibly by cointegration during transfections.
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