Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids

Lynnette Fernandez-Cuesta, Martin Peifer, Xin Lu, Ruping Sun, Luka Ozretić, Danila Seidel, Thomas Zander, Frauke Leenders, Julie George, Christian Müller, Ilona Dahmen, Berit Pinther, Graziella Bosco, Kathryn Konrad, Janine Altmüller, Peter Nürnberg, Viktor Achter, Ulrich Lang, Peter M. Schneider, Magdalena Bogus, Alex Soltermann, Odd Terje Brustugun, Åslaug Helland, Steinar Solberg, Marius Lund-Iversen, Sascha Ansén, Erich Stoelben, Gavin M. Wright, Prudence Russell, Zoe Wainer, Benjamin Solomon, John K. Field, Russell Hyde, Michael P. A. Davies, Lukas C. Heukamp, Iver Petersen, Sven Perner, Christine M. Lovly, Federico Cappuzzo, William D. Travis, Jürgen Wolf, Martin Vingron, Elisabeth Brambilla, Stefan A. Haas, Reinhard Buettner and Roman K. Thomas
Additional contact information
Lynnette Fernandez-Cuesta: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Martin Peifer: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Xin Lu: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Ruping Sun: Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics
Luka Ozretić: University Hospital Medical Center, University of Cologne
Danila Seidel: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Thomas Zander: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Frauke Leenders: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Julie George: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Christian Müller: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Ilona Dahmen: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Berit Pinther: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Graziella Bosco: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
Kathryn Konrad: Cologne Center for Genomics (CCG), University of Cologne
Janine Altmüller: Cologne Center for Genomics (CCG), University of Cologne
Peter Nürnberg: Center for Molecular Medicine Cologne (CMMC), University of Cologne
Viktor Achter: Computing Center, University of Cologne
Ulrich Lang: Computing Center, University of Cologne
Peter M. Schneider: Institute of Legal Medicine, University of Cologne
Magdalena Bogus: Institute of Legal Medicine, University of Cologne
Alex Soltermann: Institute for Surgical Pathology, University Hospital Zurich
Odd Terje Brustugun: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo
Åslaug Helland: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo
Steinar Solberg: Rikshospitalet, Oslo University Hospital
Marius Lund-Iversen: Norwegian Radium Hospital, Oslo University Hospital
Sascha Ansén: Center of Integrated Oncology Ko¨ln-Bonn, University of Cologne
Erich Stoelben: Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Ko¨ln gGmbH
Gavin M. Wright: St Vincent’s Hospital, University of Melbourne
Prudence Russell: St Vincent’s Hospital
Zoe Wainer: St Vincent’s Hospital, University of Melbourne
Benjamin Solomon: Peter MacCallum Cancer Centre
John K. Field: Roy Castle Lung Cancer Research Programme, Institute of Translational Medicine, University of Liverpool Cancer Research Centre
Russell Hyde: Roy Castle Lung Cancer Research Programme, Institute of Translational Medicine, University of Liverpool Cancer Research Centre
Michael P. A. Davies: Roy Castle Lung Cancer Research Programme, Institute of Translational Medicine, University of Liverpool Cancer Research Centre
Lukas C. Heukamp: University Hospital Medical Center, University of Cologne
Iver Petersen: Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University
Sven Perner: Institute of Pathology, University Hospital of Bonn
Christine M. Lovly: Vanderbilt-Ingram Cancer Center
Federico Cappuzzo: Istituto Toscano Tumouri
William D. Travis: Memorial Sloan Kettering Cancer Center
Jürgen Wolf: Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne—Bonn, University of Cologne
Martin Vingron: Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics
Elisabeth Brambilla: CHU Grenoble INSERM U823, Institute Albert Bonniot 38043
Stefan A. Haas: Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics
Reinhard Buettner: University Hospital Medical Center, University of Cologne
Roman K. Thomas: Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne

Nature Communications, 2014, vol. 5, issue 1, 1-7

Abstract: Abstract Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours have not been systematically studied so far. Here we perform gene copy number analysis (n=54), genome/exome (n=44) and transcriptome (n=69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodelling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40 and 22.2% of the cases, respectively, with MEN1, PSIP1 and ARID1A being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine lung tumours, TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumours but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatin-remodelling genes is sufficient to drive transformation in pulmonary carcinoids.

Date: 2014
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DOI: 10.1038/ncomms4518

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