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Identification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing.

Ian J Majewski ,
Lorenza Mittempergher ,
Nadia M Davidson ,
Astrid Bosma ,
Stefan M Willems ,
Hugo M Horlings ,
Iris de Rink ,
Liliana Greger ,
Gerrit K J Hooijer ,
Dennis Peters ,
Petra M Nederlof ,
Ingrid Hofland ,
Jeroen de Jong ,
Jelle Wesseling ,
Roelof J C Kluin ,
Wim Brugman ,
Ron Kerkhoven ,
Frank Nieboer ,
Paul Roepman ,
Annegien Broeks ,
Thomas R Muley ,
Jacek Jassem ,
Jacek Niklinski ,
Nico van Zandwijk ,
Alvis Brazma ,
Alicia Oshlack ,
Michel van den Heuvel ,
René Bernards

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.

More about this publication

The Journal of pathology

Volume 230
Issue nr. 3
Pages 270-6
Publication date 01-07-2013

Full text links

Publisher website (DOI) 10.1002/path.4209
Europe PubMed Central 23661334
Pubmed 23661334

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