title: Identification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing.
abstract: Oncogenic fusion genes that involve kinases have proven to be effective targets for therapy in a wide range of cancers. Unfortunately, the diagnostic approaches required to identify these events are struggling to keep pace with the diverse array of genetic alterations that occur in cancer. Diagnostic screening in solid tumours is particularly challenging, as many fusion genes occur with a low frequency. To overcome these limitations, we developed a capture enrichment strategy to enable high-throughput transcript sequencing of the human kinome. This approach provides a global overview of kinase fusion events, irrespective of the identity of the fusion partner. To demonstrate the utility of this system, we profiled 100 non-small cell lung cancers and identified numerous genetic alterations impacting fibroblast growth factor receptor 3 (FGFR3) in lung squamous cell carcinoma and a novel ALK fusion partner in lung adenocarcinoma.
authors: Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors: Ian J
authors: IJ
authors: Majewski
authors: Lorenza
authors: L
authors: Mittempergher
authors: Nadia M
authors: NM
authors: Davidson
authors: Astrid
authors: A
authors: Bosma
authors: Stefan M
authors: SM
authors: Willems
authors: Hugo M
authors: HM
authors: Horlings
authors: Iris
authors: I
authors: de Rink
authors: Liliana
authors: L
authors: Greger
authors: Gerrit K J
authors: GK
authors: Hooijer
authors: Dennis
authors: D
authors: Peters
authors: Petra M
authors: PM
authors: Nederlof
authors: Ingrid
authors: I
authors: Hofland
authors: Jeroen
authors: J
authors: de Jong
authors: Jelle
authors: J
authors: Wesseling
authors: Roelof J C
authors: RJ
authors: Kluin
authors: Wim
authors: W
authors: Brugman
authors: Ron
authors: R
authors: Kerkhoven
authors: Frank
authors: F
authors: Nieboer
authors: Paul
authors: P
authors: Roepman
authors: Annegien
authors: A
authors: Broeks
authors: Thomas R
authors: TR
authors: Muley
authors: Jacek
authors: J
authors: Jassem
authors: Jacek
authors: J
authors: Niklinski
authors: Nico
authors: N
authors: van Zandwijk
authors: Alvis
authors: A
authors: Brazma
authors: Alicia
authors: A
authors: Oshlack
authors: Michel
authors: M
authors: van den Heuvel
authors: René
authors: R
authors: Bernards
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D001483:Base Sequence; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005091:Exons; D015723:Gene Library; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D017423:Sequence Analysis, RNA
chemical_list: D002148:Calmodulin-Binding Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; C491925:STRN protein, human; C120551:TACC3 protein, human; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C496365:FGFR3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3