Identification of recurrent <i><scp>FGFR3</scp></i> fusion genes in lung cancer through kinome‐centred <scp>RNA</scp> sequencing

Ian J. Majewski(Walter and Eliza Hall Institute of Medical Research), Lorenza Mittempergher(The Netherlands Cancer Institute), N. Davidson(Royal Children's Hospital), Astrid Bosma(The Netherlands Cancer Institute), Stefan M. Willems(University Medical Center Utrecht), Hugo M. Horlings(Amsterdam UMC Location University of Amsterdam), Iris de Rink(The Netherlands Cancer Institute), Liliana Greger(European Bioinformatics Institute), Gerrit K. Hooijer(Amsterdam UMC Location University of Amsterdam), Dennis Peters(The Netherlands Cancer Institute), Petra M. Nederlof(The Netherlands Cancer Institute), Ingrid Hofland(The Netherlands Cancer Institute), Jeroen de Jong(The Netherlands Cancer Institute), Jelle Wesseling(The Netherlands Cancer Institute), Roelof J.C. Kluin(The Netherlands Cancer Institute), Wim Brugman(The Netherlands Cancer Institute), Ron Kerkhoven(The Netherlands Cancer Institute), Frank Nieboer(Agendia (Netherlands)), Paul Roepman(Agendia (Netherlands)), Annegien Broeks(The Netherlands Cancer Institute), Thomas R Muley(Heidelberg University), Jacek Jassem(Gdańsk Medical University), Jacek Nikliński(Medical University of Białystok), Nico van Zandwijk(Asbestos Diseases Research Institute), Alvis Brāzma(European Bioinformatics Institute), Alicia Oshlack(Royal Children's Hospital), Michel M. van den Heuvel(The Netherlands Cancer Institute), René Bernards(The Netherlands Cancer Institute)
The Journal of Pathology
May 9, 2013
Cited by 118Open Access
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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.


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