Publication

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

Majewski, I. J., Mittempergher, L., Davidson, N. M., Bosma, A., Willems, S. M., Horlings, H. M., de Rink, I., Greger, L., Hooijer, G. K. J., Peters, D., Nederlof, P. M., Hofland, I., de Jong, J., Wesseling, J., Kluin, R. J. C., Brugman, W., Kerkhoven, R., Nieboer, F., Roepman, P., Broeks, A., Muley, T. R., Jassem, J., Niklinski, J., van Zandwijk, N., Brazma, A., Oshlack, A., van den Heuvel, M. & Bernards, R., Jul-2013, In : JOURNAL OF PATHOLOGY. 230, 3, p. 270-276 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • 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

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.

Original languageEnglish
Pages (from-to)270-276
Number of pages7
JournalJOURNAL OF PATHOLOGY
Volume230
Issue number3
Publication statusPublished - Jul-2013
Externally publishedYes

    Keywords

  • Adenocarcinoma/genetics, Adenocarcinoma of Lung, Anaplastic Lymphoma Kinase, Base Sequence, Calmodulin-Binding Proteins/genetics, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Squamous Cell/genetics, Cohort Studies, Exons, Gene Library, High-Throughput Nucleotide Sequencing, Humans, In Situ Hybridization, Fluorescence, Lung Neoplasms/genetics, Membrane Proteins/genetics, Microtubule-Associated Proteins/genetics, Mutation, Nerve Tissue Proteins/genetics, Oncogene Proteins, Fusion/genetics, Receptor Protein-Tyrosine Kinases/genetics, Receptor, Fibroblast Growth Factor, Type 3/genetics, Sequence Analysis, RNA

ID: 124023550