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Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids

Author

Listed:
  • 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
    Center for Molecular Medicine Cologne (CMMC), 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
    Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne—Bonn, University of Cologne)

  • Thomas Zander

    (Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
    Center of Integrated Oncology Ko¨ln-Bonn, University of Cologne
    Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn)

  • Frauke Leenders

    (Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
    Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne—Bonn, 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
    Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
    Institute of Human Genetics, University of Cologne)

  • Peter Nürnberg

    (Center for Molecular Medicine Cologne (CMMC), University of Cologne
    Cologne Center for Genomics (CCG), University of Cologne
    Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne)

  • Viktor Achter

    (Computing Center, University of Cologne)

  • Ulrich Lang

    (Computing Center, University of Cologne
    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
    Norwegian Radium Hospital, Oslo University Hospital)

  • Åslaug Helland

    (Institute of Clinical Medicine, Faculty of Medicine, University of Oslo
    Norwegian Radium Hospital, Oslo University Hospital)

  • 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
    Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn)

  • 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
    Center of Integrated Oncology Ko¨ln-Bonn, University of Cologne
    Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn)

  • 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
    Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne—Bonn, University of Cologne
    Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn)

  • Roman K. Thomas

    (Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
    University Hospital Medical Center, University of Cologne
    Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne—Bonn, University of Cologne)

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.

Suggested Citation

  • 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 & Graz, 2014. "Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids," Nature Communications, Nature, vol. 5(1), pages 1-7, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4518
    DOI: 10.1038/ncomms4518
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