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

doi:10.1002/path.4209

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

J Pathol. 2013 Jul;230(3):270-6. doi: 10.1002/path.4209.

Affiliation

¹ Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

PMID: 23661334
DOI: 10.1002/path.4209

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / genetics*
Adenocarcinoma / pathology
Adenocarcinoma of Lung
Anaplastic Lymphoma Kinase
Base Sequence
Calmodulin-Binding Proteins / genetics
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / pathology
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / pathology
Cohort Studies
Exons
Gene Library
High-Throughput Nucleotide Sequencing
Humans
In Situ Hybridization, Fluorescence
Lung Neoplasms / genetics*
Lung Neoplasms / pathology
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

Substances

Calmodulin-Binding Proteins
Membrane Proteins
Microtubule-Associated Proteins
Nerve Tissue Proteins
Oncogene Proteins, Fusion
STRN protein, human
TACC3 protein, human
ALK protein, human
Anaplastic Lymphoma Kinase
FGFR3 protein, human
Receptor Protein-Tyrosine Kinases
Receptor, Fibroblast Growth Factor, Type 3