Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids
Identifieur interne : 001585 ( Pmc/Checkpoint ); précédent : 001584; suivant : 001586Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids
Auteurs : Lynnette Fernandez-Cuesta [Allemagne] ; Martin Peifer [Allemagne] ; Xin Lu [Allemagne] ; Ruping Sun [Allemagne] ; Luka Ozreti [Allemagne] ; Danila Seidal [Allemagne] ; Thomas Zander [Allemagne] ; Frauke Leenders [Allemagne] ; Julie George [Allemagne] ; Christian Müller [Allemagne] ; Ilona Dahmen [Allemagne] ; Berit Pinther [Allemagne] ; Graziella Bosco [Allemagne] ; Kathryn Konrad [Allemagne] ; Janine Altmüller [Allemagne] ; Peter Nürnberg [Allemagne] ; Viktor Achter [Allemagne] ; Ulrich Lang [Allemagne] ; Peter M. Schneider [Allemagne] ; Magdalena Bogus [Allemagne] ; Alex Soltermann [Suisse] ; Odd Terje Brustugun [Norvège] ; Slaug Helland [Norvège] ; Steinar Solberg [Norvège] ; Marius Lund-Iversen [Norvège] ; Sascha Ansén [Allemagne] ; Erich Stoelben [Allemagne] ; Gavin M. Wright [Australie] ; Prudence Russell [Australie] ; Zoe Wainer [Australie] ; Benjamin Solomon [Australie] ; John K. Field [Royaume-Uni] ; Russell Hyde [Royaume-Uni] ; Michael Pa. Davies [Royaume-Uni] ; Lukas C. Heukamp [Allemagne] ; Iver Petersen [Allemagne] ; Sven Perner [Allemagne] ; Christine Lovly [États-Unis] ; Federico Cappuzzo [Italie] ; William D. Travis [États-Unis] ; Jürgen Wolf [Allemagne] ; Martin Vingron [Allemagne] ; Elisabeth Brambilla [France] ; Stefan A. Haas [Allemagne] ; Reinhard Buettner [Allemagne] ; Roman K. Thomas [Allemagne]Source :
- Nature communications [ 2041-1723 ] ; 2014.
Abstract
Pulmonary carcinoids are rare neuroendocrine tumors of the lung. The molecular alterations underlying the pathogenesis of these tumors 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-remodeling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40% and 22.2% of the cases respectively, with
Url:
DOI: 10.1038/ncomms4518
PubMed: 24670920
PubMed Central: 4132974
Affiliations:
- Allemagne, Australie, France, Italie, Norvège, Royaume-Uni, Suisse, États-Unis
- Berlin, District de Cologne, Rhénanie-du-Nord-Westphalie, Tennessee
- Berlin, Bonn, Cologne
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wicri:level="3"><nlm:aff id="A3">Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Ozreti, Luka" sort="Ozreti, Luka" uniqKey="Ozreti L" first="Luka" last="Ozreti">Luka Ozreti</name><affiliation wicri:level="3"><nlm:aff id="A4">Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne</wicri:regionArea><placeName><region type="land" 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of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Zander, Thomas" sort="Zander, Thomas" uniqKey="Zander T" first="Thomas" last="Zander">Thomas Zander</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A6">Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A7">Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Leenders, Frauke" sort="Leenders, Frauke" uniqKey="Leenders F" first="Frauke" last="Leenders">Frauke Leenders</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A5">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="George, Julie" sort="George, Julie" uniqKey="George J" first="Julie" last="George">Julie George</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Muller, Christian" sort="Muller, Christian" uniqKey="Muller C" first="Christian" last="Müller">Christian Müller</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Dahmen, Ilona" sort="Dahmen, Ilona" uniqKey="Dahmen I" first="Ilona" last="Dahmen">Ilona Dahmen</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Pinther, Berit" sort="Pinther, Berit" uniqKey="Pinther B" first="Berit" last="Pinther">Berit Pinther</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Bosco, Graziella" sort="Bosco, Graziella" uniqKey="Bosco G" first="Graziella" last="Bosco">Graziella Bosco</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Konrad, Kathryn" sort="Konrad, Kathryn" uniqKey="Konrad K" first="Kathryn" last="Konrad">Kathryn Konrad</name><affiliation wicri:level="1"><nlm:aff id="A8">Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Cologne Center for Genomics (CCG), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name><affiliation wicri:level="1"><nlm:aff id="A8">Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Cologne Center for Genomics (CCG), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="A10">Institute of Human Genetics, University of Cologne, Cologne 50931, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Human Genetics, University of Cologne, Cologne 50931</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Nurnberg, Peter" sort="Nurnberg, Peter" uniqKey="Nurnberg P" first="Peter" last="Nürnberg">Peter Nürnberg</name><affiliation wicri:level="1"><nlm:aff id="A2">Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Cologne Center for Genomics (CCG), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Achter, Viktor" sort="Achter, Viktor" uniqKey="Achter V" first="Viktor" last="Achter">Viktor Achter</name><affiliation wicri:level="3"><nlm:aff id="A11">Computing Center, University of Cologne, 50931 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computing Center, University of Cologne, 50931 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Lang, Ulrich" sort="Lang, Ulrich" uniqKey="Lang U" first="Ulrich" last="Lang">Ulrich Lang</name><affiliation wicri:level="3"><nlm:aff id="A11">Computing Center, University of Cologne, 50931 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computing Center, University of Cologne, 50931 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A12">Department of Informatics, University of Cologne, 50931 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Informatics, University of Cologne, 50931 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Schneider, Peter M" sort="Schneider, Peter M" uniqKey="Schneider P" first="Peter M" last="Schneider">Peter M. Schneider</name><affiliation wicri:level="3"><nlm:aff id="A13">Institute of Legal Medicine, University of Cologne, 50823 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Legal Medicine, University of Cologne, 50823 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Bogus, Magdalena" sort="Bogus, Magdalena" uniqKey="Bogus M" first="Magdalena" last="Bogus">Magdalena Bogus</name><affiliation wicri:level="3"><nlm:aff id="A13">Institute of Legal Medicine, University of Cologne, 50823 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Legal Medicine, University of Cologne, 50823 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Soltermann, Alex" sort="Soltermann, Alex" uniqKey="Soltermann A" first="Alex" last="Soltermann">Alex Soltermann</name><affiliation wicri:level="1"><nlm:aff id="A14">Institute for Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute for Surgical Pathology, University Hospital Zurich, 8091 Zurich</wicri:regionArea><wicri:noRegion>8091 Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Brustugun, Odd Terje" sort="Brustugun, Odd Terje" uniqKey="Brustugun O" first="Odd Terje" last="Brustugun">Odd Terje Brustugun</name><affiliation wicri:level="1"><nlm:aff id="A15">Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo</wicri:regionArea><wicri:noRegion>N-0424 Oslo</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A16">Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo</wicri:regionArea><wicri:noRegion>N-0310 Oslo</wicri:noRegion></affiliation></author><author><name sortKey="Helland, Slaug" sort="Helland, Slaug" uniqKey="Helland " first=" Slaug" last="Helland"> Slaug Helland</name><affiliation wicri:level="1"><nlm:aff id="A15">Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo</wicri:regionArea><wicri:noRegion>N-0424 Oslo</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A16">Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo</wicri:regionArea><wicri:noRegion>N-0310 Oslo</wicri:noRegion></affiliation></author><author><name sortKey="Solberg, Steinar" sort="Solberg, Steinar" uniqKey="Solberg S" first="Steinar" last="Solberg">Steinar Solberg</name><affiliation wicri:level="1"><nlm:aff id="A17">Department of Thoracic Surgery, Rikshospitalet, Oslo University Hospital, N-0027 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of Thoracic Surgery, Rikshospitalet, Oslo University Hospital, N-0027 Oslo</wicri:regionArea><wicri:noRegion>N-0027 Oslo</wicri:noRegion></affiliation></author><author><name sortKey="Lund Iversen, Marius" sort="Lund Iversen, Marius" uniqKey="Lund Iversen M" first="Marius" last="Lund-Iversen">Marius Lund-Iversen</name><affiliation wicri:level="1"><nlm:aff id="A18">Department of pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo</wicri:regionArea><wicri:noRegion>N-0310 Oslo</wicri:noRegion></affiliation></author><author><name sortKey="Ansen, Sascha" sort="Ansen, Sascha" uniqKey="Ansen S" first="Sascha" last="Ansén">Sascha Ansén</name><affiliation wicri:level="3"><nlm:aff id="A6">Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Stoelben, Erich" sort="Stoelben, Erich" uniqKey="Stoelben E" first="Erich" last="Stoelben">Erich Stoelben</name><affiliation wicri:level="3"><nlm:aff id="A19">Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, 51109 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, 51109 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Wright, Gavin M" sort="Wright, Gavin M" uniqKey="Wright G" first="Gavin M." last="Wright">Gavin M. Wright</name><affiliation wicri:level="1"><nlm:aff id="A20">University of Melbourne Department of Surgery, St Vincent’s Hospital, Melbourne, 3065 Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Melbourne Department of Surgery, St Vincent’s Hospital, Melbourne, 3065 Victoria</wicri:regionArea><wicri:noRegion>3065 Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Russell, Prudence" sort="Russell, Prudence" uniqKey="Russell P" first="Prudence" last="Russell">Prudence Russell</name><affiliation wicri:level="1"><nlm:aff id="A21">Department of Pathology, St. Vincent’s Hospital, Melbourne, 3065 Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, St. Vincent’s Hospital, Melbourne, 3065 Victoria</wicri:regionArea><wicri:noRegion>3065 Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Wainer, Zoe" sort="Wainer, Zoe" uniqKey="Wainer Z" first="Zoe" last="Wainer">Zoe Wainer</name><affiliation wicri:level="1"><nlm:aff id="A20">University of Melbourne Department of Surgery, St Vincent’s Hospital, Melbourne, 3065 Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Melbourne Department of Surgery, St Vincent’s Hospital, Melbourne, 3065 Victoria</wicri:regionArea><wicri:noRegion>3065 Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Solomon, Benjamin" sort="Solomon, Benjamin" uniqKey="Solomon B" first="Benjamin" last="Solomon">Benjamin Solomon</name><affiliation wicri:level="1"><nlm:aff id="A22">Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, 3002 Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, 3002 Victoria</wicri:regionArea><wicri:noRegion>3002 Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Field, John K" sort="Field, John K" uniqKey="Field J" first="John K" last="Field">John K. Field</name><affiliation wicri:level="1"><nlm:aff id="A23">Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA</wicri:regionArea><wicri:noRegion>L3 9TA</wicri:noRegion></affiliation></author><author><name sortKey="Hyde, Russell" sort="Hyde, Russell" uniqKey="Hyde R" first="Russell" last="Hyde">Russell Hyde</name><affiliation wicri:level="1"><nlm:aff id="A23">Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA</wicri:regionArea><wicri:noRegion>L3 9TA</wicri:noRegion></affiliation></author><author><name sortKey="Davies, Michael Pa" sort="Davies, Michael Pa" uniqKey="Davies M" first="Michael Pa." last="Davies">Michael Pa. Davies</name><affiliation wicri:level="1"><nlm:aff id="A23">Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA</wicri:regionArea><wicri:noRegion>L3 9TA</wicri:noRegion></affiliation></author><author><name sortKey="Heukamp, Lukas C" sort="Heukamp, Lukas C" uniqKey="Heukamp L" first="Lukas C" last="Heukamp">Lukas C. Heukamp</name><affiliation wicri:level="3"><nlm:aff id="A4">Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A7">Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Petersen, Iver" sort="Petersen, Iver" uniqKey="Petersen I" first="Iver" last="Petersen">Iver Petersen</name><affiliation wicri:level="1"><nlm:aff id="A24">Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, 07743 Jena, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, 07743 Jena</wicri:regionArea><wicri:noRegion>07743 Jena</wicri:noRegion><wicri:noRegion>07743 Jena</wicri:noRegion><wicri:noRegion>07743 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Perner, Sven" sort="Perner, Sven" uniqKey="Perner S" first="Sven" last="Perner">Sven Perner</name><affiliation wicri:level="3"><nlm:aff id="A25">Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, 53127 Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Lovly, Christine" sort="Lovly, Christine" uniqKey="Lovly C" first="Christine" last="Lovly">Christine Lovly</name><affiliation wicri:level="2"><nlm:aff id="A26">Vanderbilt-Ingram Cancer Center, Nashville, TN37232, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vanderbilt-Ingram Cancer Center, Nashville, TN37232</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Cappuzzo, Federico" sort="Cappuzzo, Federico" uniqKey="Cappuzzo F" first="Federico" last="Cappuzzo">Federico Cappuzzo</name><affiliation wicri:level="1"><nlm:aff id="A27">Department of Medical Oncology, Istituto Toscano Tumouri, 57100 Livorno, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medical Oncology, Istituto Toscano Tumouri, 57100 Livorno</wicri:regionArea><wicri:noRegion>57100 Livorno</wicri:noRegion></affiliation></author><author><name sortKey="Travis, William D" sort="Travis, William D" uniqKey="Travis W" first="William D" last="Travis">William D. Travis</name><affiliation wicri:level="1"><nlm:aff id="A28">Department of Pathology, Memorial Sloan Kettering Cancer Center, New York 10065, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Memorial Sloan Kettering Cancer Center, New York 10065</wicri:regionArea><wicri:noRegion>New York 10065</wicri:noRegion></affiliation></author><author><name sortKey="Wolf, Jurgen" sort="Wolf, Jurgen" uniqKey="Wolf J" first="Jürgen" last="Wolf">Jürgen Wolf</name><affiliation wicri:level="3"><nlm:aff id="A5">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A6">Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A7">Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Vingron, Martin" sort="Vingron, Martin" uniqKey="Vingron M" first="Martin" last="Vingron">Martin Vingron</name><affiliation wicri:level="3"><nlm:aff id="A3">Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Brambilla, Elisabeth" sort="Brambilla, Elisabeth" uniqKey="Brambilla E" first="Elisabeth" last="Brambilla">Elisabeth Brambilla</name><affiliation wicri:level="1"><nlm:aff id="A29">Department of Pathology, CHU Grenoble INSERM U823, Institute Albert Bonniot 38043 CS10217 Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Pathology, CHU Grenoble INSERM U823, Institute Albert Bonniot 38043 CS10217 Grenoble</wicri:regionArea><wicri:noRegion>38043 CS10217 Grenoble</wicri:noRegion><wicri:noRegion>38043 CS10217 Grenoble</wicri:noRegion></affiliation></author><author><name sortKey="Haas, Stefan A" sort="Haas, Stefan A" uniqKey="Haas S" first="Stefan A." last="Haas">Stefan A. Haas</name><affiliation wicri:level="3"><nlm:aff id="A3">Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Buettner, Reinhard" sort="Buettner, Reinhard" uniqKey="Buettner R" first="Reinhard" last="Buettner">Reinhard Buettner</name><affiliation wicri:level="3"><nlm:aff id="A4">Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A5">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A7">Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Thomas, Roman K" sort="Thomas, Roman K" uniqKey="Thomas R" first="Roman K" last="Thomas">Roman K. Thomas</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A4">Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A5">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24670920</idno><idno type="pmc">4132974</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132974</idno><idno type="RBID">PMC:4132974</idno><idno type="doi">10.1038/ncomms4518</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">002D85</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002D85</idno><idno type="wicri:Area/Pmc/Curation">002C35</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002C35</idno><idno type="wicri:Area/Pmc/Checkpoint">001585</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001585</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids</title><author><name sortKey="Fernandez Cuesta, Lynnette" sort="Fernandez Cuesta, Lynnette" uniqKey="Fernandez Cuesta L" first="Lynnette" last="Fernandez-Cuesta">Lynnette Fernandez-Cuesta</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Peifer, Martin" sort="Peifer, Martin" uniqKey="Peifer M" first="Martin" last="Peifer">Martin Peifer</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Lu, Xin" sort="Lu, Xin" uniqKey="Lu X" first="Xin" last="Lu">Xin Lu</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Sun, Ruping" sort="Sun, Ruping" uniqKey="Sun R" first="Ruping" last="Sun">Ruping Sun</name><affiliation wicri:level="3"><nlm:aff id="A3">Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Ozreti, Luka" sort="Ozreti, Luka" uniqKey="Ozreti L" first="Luka" last="Ozreti">Luka Ozreti</name><affiliation wicri:level="3"><nlm:aff id="A4">Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Seidal, Danila" sort="Seidal, Danila" uniqKey="Seidal D" first="Danila" last="Seidal">Danila Seidal</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A5">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Zander, Thomas" sort="Zander, Thomas" uniqKey="Zander T" first="Thomas" last="Zander">Thomas Zander</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A6">Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A7">Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Leenders, Frauke" sort="Leenders, Frauke" uniqKey="Leenders F" first="Frauke" last="Leenders">Frauke Leenders</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A5">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="George, Julie" sort="George, Julie" uniqKey="George J" first="Julie" last="George">Julie George</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Muller, Christian" sort="Muller, Christian" uniqKey="Muller C" first="Christian" last="Müller">Christian Müller</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Dahmen, Ilona" sort="Dahmen, Ilona" uniqKey="Dahmen I" first="Ilona" last="Dahmen">Ilona Dahmen</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Pinther, Berit" sort="Pinther, Berit" uniqKey="Pinther B" first="Berit" last="Pinther">Berit Pinther</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Bosco, Graziella" sort="Bosco, Graziella" uniqKey="Bosco G" first="Graziella" last="Bosco">Graziella Bosco</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Konrad, Kathryn" sort="Konrad, Kathryn" uniqKey="Konrad K" first="Kathryn" last="Konrad">Kathryn Konrad</name><affiliation wicri:level="1"><nlm:aff id="A8">Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Cologne Center for Genomics (CCG), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name><affiliation wicri:level="1"><nlm:aff id="A8">Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Cologne Center for Genomics (CCG), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="A10">Institute of Human Genetics, University of Cologne, Cologne 50931, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Human Genetics, University of Cologne, Cologne 50931</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Nurnberg, Peter" sort="Nurnberg, Peter" uniqKey="Nurnberg P" first="Peter" last="Nürnberg">Peter Nürnberg</name><affiliation wicri:level="1"><nlm:aff id="A2">Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Cologne Center for Genomics (CCG), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Achter, Viktor" sort="Achter, Viktor" uniqKey="Achter V" first="Viktor" last="Achter">Viktor Achter</name><affiliation wicri:level="3"><nlm:aff id="A11">Computing Center, University of Cologne, 50931 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computing Center, University of Cologne, 50931 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Lang, Ulrich" sort="Lang, Ulrich" uniqKey="Lang U" first="Ulrich" last="Lang">Ulrich Lang</name><affiliation wicri:level="3"><nlm:aff id="A11">Computing Center, University of Cologne, 50931 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computing Center, University of Cologne, 50931 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A12">Department of Informatics, University of Cologne, 50931 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Informatics, University of Cologne, 50931 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Schneider, Peter M" sort="Schneider, Peter M" uniqKey="Schneider P" first="Peter M" last="Schneider">Peter M. Schneider</name><affiliation wicri:level="3"><nlm:aff id="A13">Institute of Legal Medicine, University of Cologne, 50823 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Legal Medicine, University of Cologne, 50823 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Bogus, Magdalena" sort="Bogus, Magdalena" uniqKey="Bogus M" first="Magdalena" last="Bogus">Magdalena Bogus</name><affiliation wicri:level="3"><nlm:aff id="A13">Institute of Legal Medicine, University of Cologne, 50823 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Legal Medicine, University of Cologne, 50823 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Soltermann, Alex" sort="Soltermann, Alex" uniqKey="Soltermann A" first="Alex" last="Soltermann">Alex Soltermann</name><affiliation wicri:level="1"><nlm:aff id="A14">Institute for Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute for Surgical Pathology, University Hospital Zurich, 8091 Zurich</wicri:regionArea><wicri:noRegion>8091 Zurich</wicri:noRegion></affiliation></author><author><name sortKey="Brustugun, Odd Terje" sort="Brustugun, Odd Terje" uniqKey="Brustugun O" first="Odd Terje" last="Brustugun">Odd Terje Brustugun</name><affiliation wicri:level="1"><nlm:aff id="A15">Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo</wicri:regionArea><wicri:noRegion>N-0424 Oslo</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A16">Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo</wicri:regionArea><wicri:noRegion>N-0310 Oslo</wicri:noRegion></affiliation></author><author><name sortKey="Helland, Slaug" sort="Helland, Slaug" uniqKey="Helland " first=" Slaug" last="Helland"> Slaug Helland</name><affiliation wicri:level="1"><nlm:aff id="A15">Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo</wicri:regionArea><wicri:noRegion>N-0424 Oslo</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A16">Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo</wicri:regionArea><wicri:noRegion>N-0310 Oslo</wicri:noRegion></affiliation></author><author><name sortKey="Solberg, Steinar" sort="Solberg, Steinar" uniqKey="Solberg S" first="Steinar" last="Solberg">Steinar Solberg</name><affiliation wicri:level="1"><nlm:aff id="A17">Department of Thoracic Surgery, Rikshospitalet, Oslo University Hospital, N-0027 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of Thoracic Surgery, Rikshospitalet, Oslo University Hospital, N-0027 Oslo</wicri:regionArea><wicri:noRegion>N-0027 Oslo</wicri:noRegion></affiliation></author><author><name sortKey="Lund Iversen, Marius" sort="Lund Iversen, Marius" uniqKey="Lund Iversen M" first="Marius" last="Lund-Iversen">Marius Lund-Iversen</name><affiliation wicri:level="1"><nlm:aff id="A18">Department of pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo</wicri:regionArea><wicri:noRegion>N-0310 Oslo</wicri:noRegion></affiliation></author><author><name sortKey="Ansen, Sascha" sort="Ansen, Sascha" uniqKey="Ansen S" first="Sascha" last="Ansén">Sascha Ansén</name><affiliation wicri:level="3"><nlm:aff id="A6">Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Stoelben, Erich" sort="Stoelben, Erich" uniqKey="Stoelben E" first="Erich" last="Stoelben">Erich Stoelben</name><affiliation wicri:level="3"><nlm:aff id="A19">Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, 51109 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, 51109 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Wright, Gavin M" sort="Wright, Gavin M" uniqKey="Wright G" first="Gavin M." last="Wright">Gavin M. Wright</name><affiliation wicri:level="1"><nlm:aff id="A20">University of Melbourne Department of Surgery, St Vincent’s Hospital, Melbourne, 3065 Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Melbourne Department of Surgery, St Vincent’s Hospital, Melbourne, 3065 Victoria</wicri:regionArea><wicri:noRegion>3065 Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Russell, Prudence" sort="Russell, Prudence" uniqKey="Russell P" first="Prudence" last="Russell">Prudence Russell</name><affiliation wicri:level="1"><nlm:aff id="A21">Department of Pathology, St. Vincent’s Hospital, Melbourne, 3065 Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, St. Vincent’s Hospital, Melbourne, 3065 Victoria</wicri:regionArea><wicri:noRegion>3065 Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Wainer, Zoe" sort="Wainer, Zoe" uniqKey="Wainer Z" first="Zoe" last="Wainer">Zoe Wainer</name><affiliation wicri:level="1"><nlm:aff id="A20">University of Melbourne Department of Surgery, St Vincent’s Hospital, Melbourne, 3065 Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Melbourne Department of Surgery, St Vincent’s Hospital, Melbourne, 3065 Victoria</wicri:regionArea><wicri:noRegion>3065 Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Solomon, Benjamin" sort="Solomon, Benjamin" uniqKey="Solomon B" first="Benjamin" last="Solomon">Benjamin Solomon</name><affiliation wicri:level="1"><nlm:aff id="A22">Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, 3002 Victoria, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, 3002 Victoria</wicri:regionArea><wicri:noRegion>3002 Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Field, John K" sort="Field, John K" uniqKey="Field J" first="John K" last="Field">John K. Field</name><affiliation wicri:level="1"><nlm:aff id="A23">Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA</wicri:regionArea><wicri:noRegion>L3 9TA</wicri:noRegion></affiliation></author><author><name sortKey="Hyde, Russell" sort="Hyde, Russell" uniqKey="Hyde R" first="Russell" last="Hyde">Russell Hyde</name><affiliation wicri:level="1"><nlm:aff id="A23">Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA</wicri:regionArea><wicri:noRegion>L3 9TA</wicri:noRegion></affiliation></author><author><name sortKey="Davies, Michael Pa" sort="Davies, Michael Pa" uniqKey="Davies M" first="Michael Pa." last="Davies">Michael Pa. Davies</name><affiliation wicri:level="1"><nlm:aff id="A23">Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA</wicri:regionArea><wicri:noRegion>L3 9TA</wicri:noRegion></affiliation></author><author><name sortKey="Heukamp, Lukas C" sort="Heukamp, Lukas C" uniqKey="Heukamp L" first="Lukas C" last="Heukamp">Lukas C. Heukamp</name><affiliation wicri:level="3"><nlm:aff id="A4">Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A7">Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Petersen, Iver" sort="Petersen, Iver" uniqKey="Petersen I" first="Iver" last="Petersen">Iver Petersen</name><affiliation wicri:level="1"><nlm:aff id="A24">Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, 07743 Jena, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, 07743 Jena</wicri:regionArea><wicri:noRegion>07743 Jena</wicri:noRegion><wicri:noRegion>07743 Jena</wicri:noRegion><wicri:noRegion>07743 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Perner, Sven" sort="Perner, Sven" uniqKey="Perner S" first="Sven" last="Perner">Sven Perner</name><affiliation wicri:level="3"><nlm:aff id="A25">Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, 53127 Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Lovly, Christine" sort="Lovly, Christine" uniqKey="Lovly C" first="Christine" last="Lovly">Christine Lovly</name><affiliation wicri:level="2"><nlm:aff id="A26">Vanderbilt-Ingram Cancer Center, Nashville, TN37232, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vanderbilt-Ingram Cancer Center, Nashville, TN37232</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Cappuzzo, Federico" sort="Cappuzzo, Federico" uniqKey="Cappuzzo F" first="Federico" last="Cappuzzo">Federico Cappuzzo</name><affiliation wicri:level="1"><nlm:aff id="A27">Department of Medical Oncology, Istituto Toscano Tumouri, 57100 Livorno, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medical Oncology, Istituto Toscano Tumouri, 57100 Livorno</wicri:regionArea><wicri:noRegion>57100 Livorno</wicri:noRegion></affiliation></author><author><name sortKey="Travis, William D" sort="Travis, William D" uniqKey="Travis W" first="William D" last="Travis">William D. Travis</name><affiliation wicri:level="1"><nlm:aff id="A28">Department of Pathology, Memorial Sloan Kettering Cancer Center, New York 10065, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Memorial Sloan Kettering Cancer Center, New York 10065</wicri:regionArea><wicri:noRegion>New York 10065</wicri:noRegion></affiliation></author><author><name sortKey="Wolf, Jurgen" sort="Wolf, Jurgen" uniqKey="Wolf J" first="Jürgen" last="Wolf">Jürgen Wolf</name><affiliation wicri:level="3"><nlm:aff id="A5">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A6">Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A7">Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Vingron, Martin" sort="Vingron, Martin" uniqKey="Vingron M" first="Martin" last="Vingron">Martin Vingron</name><affiliation wicri:level="3"><nlm:aff id="A3">Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Brambilla, Elisabeth" sort="Brambilla, Elisabeth" uniqKey="Brambilla E" first="Elisabeth" last="Brambilla">Elisabeth Brambilla</name><affiliation wicri:level="1"><nlm:aff id="A29">Department of Pathology, CHU Grenoble INSERM U823, Institute Albert Bonniot 38043 CS10217 Grenoble, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Pathology, CHU Grenoble INSERM U823, Institute Albert Bonniot 38043 CS10217 Grenoble</wicri:regionArea><wicri:noRegion>38043 CS10217 Grenoble</wicri:noRegion><wicri:noRegion>38043 CS10217 Grenoble</wicri:noRegion></affiliation></author><author><name sortKey="Haas, Stefan A" sort="Haas, Stefan A" uniqKey="Haas S" first="Stefan A." last="Haas">Stefan A. Haas</name><affiliation wicri:level="3"><nlm:aff id="A3">Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Buettner, Reinhard" sort="Buettner, Reinhard" uniqKey="Buettner R" first="Reinhard" last="Buettner">Reinhard Buettner</name><affiliation wicri:level="3"><nlm:aff id="A4">Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A5">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A7">Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author><author><name sortKey="Thomas, Roman K" sort="Thomas, Roman K" uniqKey="Thomas R" first="Roman K" last="Thomas">Roman K. Thomas</name><affiliation wicri:level="3"><nlm:aff id="A1">Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A4">Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="A5">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Cologne</settlement></placeName></affiliation></author></analytic><series><title level="j">Nature communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Pulmonary carcinoids are rare neuroendocrine tumors of the lung. The molecular alterations underlying the pathogenesis of these tumors 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-remodeling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40% and 22.2% of the cases respectively, with <italic>MEN1</italic>, <italic>PSIP1</italic> and <italic>ARID1A</italic> being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine tumors, <italic>TP53</italic> and <italic>RB1</italic> mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumors but arise through independent cellular mechanisms. 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<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101528555</journal-id><journal-id journal-id-type="pubmed-jr-id">37539</journal-id><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id><journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id><journal-title-group><journal-title>Nature communications</journal-title></journal-title-group><issn pub-type="epub">2041-1723</issn></journal-meta><article-meta><article-id pub-id-type="pmid">24670920</article-id><article-id pub-id-type="pmc">4132974</article-id><article-id pub-id-type="doi">10.1038/ncomms4518</article-id><article-id pub-id-type="manuscript">NIHMS571151</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Fernandez-Cuesta</surname><given-names>Lynnette</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Peifer</surname><given-names>Martin</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lu</surname><given-names>Xin</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Ruping</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ozretić</surname><given-names>Luka</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Seidal</surname><given-names>Danila</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Zander</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Leenders</surname><given-names>Frauke</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>George</surname><given-names>Julie</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Müller</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Dahmen</surname><given-names>Ilona</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Pinther</surname><given-names>Berit</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bosco</surname><given-names>Graziella</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Konrad</surname><given-names>Kathryn</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Altmüller</surname><given-names>Janine</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Nürnberg</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Achter</surname><given-names>Viktor</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Lang</surname><given-names>Ulrich</given-names></name><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Schneider</surname><given-names>Peter M</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Bogus</surname><given-names>Magdalena</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Soltermann</surname><given-names>Alex</given-names></name><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Brustugun</surname><given-names>Odd Terje</given-names></name><xref ref-type="aff" rid="A15">15</xref><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Helland</surname><given-names>Åslaug</given-names></name><xref ref-type="aff" rid="A15">15</xref><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Solberg</surname><given-names>Steinar</given-names></name><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Lund-Iversen</surname><given-names>Marius</given-names></name><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Ansén</surname><given-names>Sascha</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Stoelben</surname><given-names>Erich</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Wright</surname><given-names>Gavin M.</given-names></name><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Russell</surname><given-names>Prudence</given-names></name><xref ref-type="aff" rid="A21">21</xref></contrib><contrib contrib-type="author"><name><surname>Wainer</surname><given-names>Zoe</given-names></name><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Solomon</surname><given-names>Benjamin</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Field</surname><given-names>John K</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Hyde</surname><given-names>Russell</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Davies</surname><given-names>Michael PA.</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Heukamp</surname><given-names>Lukas C</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Petersen</surname><given-names>Iver</given-names></name><xref ref-type="aff" rid="A24">24</xref></contrib><contrib contrib-type="author"><name><surname>Perner</surname><given-names>Sven</given-names></name><xref ref-type="aff" rid="A25">25</xref></contrib><contrib contrib-type="author"><name><surname>Lovly</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><name><surname>Cappuzzo</surname><given-names>Federico</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Travis</surname><given-names>William D</given-names></name><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Wolf</surname><given-names>Jürgen</given-names></name><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Vingron</surname><given-names>Martin</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Brambilla</surname><given-names>Elisabeth</given-names></name><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Haas</surname><given-names>Stefan A.</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Buettner</surname><given-names>Reinhard</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Thomas</surname><given-names>Roman K</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne, Germany</aff><aff id="A2"><label>2</label>Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany</aff><aff id="A3"><label>3</label>Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany</aff><aff id="A4"><label>4</label>Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany</aff><aff id="A5"><label>5</label>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne – Bonn, University of Cologne, 50924 Cologne, Germany</aff><aff id="A6"><label>6</label>Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne, Germany</aff><aff id="A7"><label>7</label>Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany</aff><aff id="A8"><label>8</label>Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany</aff><aff id="A9"><label>9</label>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany</aff><aff id="A10"><label>10</label>Institute of Human Genetics, University of Cologne, Cologne 50931, Germany</aff><aff id="A11"><label>11</label>Computing Center, University of Cologne, 50931 Cologne, Germany</aff><aff id="A12"><label>12</label>Department of Informatics, University of Cologne, 50931 Cologne, Germany</aff><aff id="A13"><label>13</label>Institute of Legal Medicine, University of Cologne, 50823 Cologne, Germany</aff><aff id="A14"><label>14</label>Institute for Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland</aff><aff id="A15"><label>15</label>Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway</aff><aff id="A16"><label>16</label>Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway</aff><aff id="A17"><label>17</label>Department of Thoracic Surgery, Rikshospitalet, Oslo University Hospital, N-0027 Oslo, Norway</aff><aff id="A18"><label>18</label>Department of pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway</aff><aff id="A19"><label>19</label>Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, 51109 Cologne, Germany</aff><aff id="A20"><label>20</label>University of Melbourne Department of Surgery, St Vincent’s Hospital, Melbourne, 3065 Victoria, Australia</aff><aff id="A21"><label>21</label>Department of Pathology, St. Vincent’s Hospital, Melbourne, 3065 Victoria, Australia</aff><aff id="A22"><label>22</label>Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, 3002 Victoria, Australia</aff><aff id="A23"><label>23</label>Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA, UK</aff><aff id="A24"><label>24</label>Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, 07743 Jena, Germany</aff><aff id="A25"><label>25</label>Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany</aff><aff id="A26"><label>26</label>Vanderbilt-Ingram Cancer Center, Nashville, TN37232, USA</aff><aff id="A27"><label>27</label>Department of Medical Oncology, Istituto Toscano Tumouri, 57100 Livorno, Italy</aff><aff id="A28"><label>28</label>Department of Pathology, Memorial Sloan Kettering Cancer Center, New York 10065, USA</aff><aff id="A29"><label>29</label>Department of Pathology, CHU Grenoble INSERM U823, Institute Albert Bonniot 38043 CS10217 Grenoble, France</aff><author-notes><corresp id="CR1"><underline>Correspondence:</underline> Roman K Thomas, Department of Translational Genomics, University of Cologne, Weyertal 115b, 50931 Cologne, Germany, +49-221-478-98771, <email>roman.thomas@uni-Köln.de</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>23</day><month>4</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>27</day><month>3</month><year>2014</year></pub-date><pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>27</day><month>9</month><year>2014</year></pub-date><volume>5</volume><fpage>3518</fpage><lpage>3518</lpage><pmc-comment>elocation-id from pubmed: 10.1038/ncomms4518</pmc-comment>
<permissions><license xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms"><license-p>Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:<ext-link ext-link-type="uri" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</ext-link></license-p></license></permissions><abstract><p id="P1">Pulmonary carcinoids are rare neuroendocrine tumors of the lung. The molecular alterations underlying the pathogenesis of these tumors 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-remodeling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40% and 22.2% of the cases respectively, with <italic>MEN1</italic>, <italic>PSIP1</italic> and <italic>ARID1A</italic> being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine tumors, <italic>TP53</italic> and <italic>RB1</italic> mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumors but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatin remodeling genes is sufficient to drive transformation in pulmonary carcinoids.</p></abstract></article-meta></front><floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Genomic characterization of pulmonary carcinoids. (a) CIRCOS plot of the chromothripsis case. The outer ring shows chromosomes arranged end to end. Somatic copy number alterations (gains in red and losses in blue) detected by 6.0 SNP arrays are depicted in the inside ring. (<bold>b</bold>) Copy numbers and chimeric transcripts of affected chromosomes. Segmented copy number states (blue points) are shown together with raw copy number data averaged over 50 adjacent probes (grey points). To show the different levels of strength for the identified chimeric transcripts all curves are scaled according to the sequencing coverage at the fusion-point. (<bold>c</bold>) Mutation frequency detected by genome and exome sequencing in pulmonary carcinoids (PCA). Each blue dot represents the number of mutations per megabase in one pulmonary carcinoid sample. Average frequencies are also shown for adenocarcinomas (AD), squamous (SQ), and small-cell lung cancer (SCLC) base on previous studies<sup><xref rid="R2" ref-type="bibr">2</xref>,<xref rid="R4" ref-type="bibr">4</xref>,<xref rid="R5" ref-type="bibr">5</xref></sup> (<bold>d</bold>) Comparison of context independent transversion and transition rates (an overall strand symmetry is assumed) between rates derived from molecular evolution (evol)<sup><xref rid="R36" ref-type="bibr">36</xref></sup>, from a previous SCLC sequencing study<sup><xref rid="R2" ref-type="bibr">2</xref></sup>, and from the pulmonary carcinoids (PCA) genome and exome sequencing. All rates are scaled as such that their overall sum is one.</p></caption><graphic xlink:href="nihms-571151-f0001"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Significant affected genes and pathways in pulmonary carcinoids. (a) Significantly mutated genes and pathways identified by genome (n=29), exome (n=15) and transcriptome (n=69) sequencing. The percentage of pulmonary carcinoids with a specific gene or pathway mutated is noted at the right side. The <italic>q</italic>-values of the significantly mutated genes and pathways are shown in brackets (see Methods section). Samples are displayed as columns and arranged to emphasize mutually exclusive mutations. (<bold>b</bold>) Methylation levels of H3K9me3 and H3K27me3 in pulmonary carcinoids. Representative pictures of different degrees of methylation (high, intermediate, and low) for some of the samples summarized in <xref ref-type="table" rid="T1">Table 1</xref>. The mutated gene is shown in italics at the bottom right part of the correspondent picture. Wild-type samples are denoted by WT.</p></caption><graphic xlink:href="nihms-571151-f0002"></graphic></fig><fig id="F3" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Expression data analysis of pulmonary carcinois based on RNAseq data. (a) Consensus Kmeans clustering<sup><xref rid="R32" ref-type="bibr">32</xref>,<xref rid="R33" ref-type="bibr">33</xref></sup> using RNAseq expression data of 50 adenocarcinomas (AD, in blue), 42 small-cell lung cancer (SCLC, in red), and 69 pulmonary carcinoids (PCA, in purple) identified 3 groups using the clustering module from GenePattern<sup><xref rid="R31" ref-type="bibr">31</xref></sup> and consensus CDF<sup><xref rid="R32" ref-type="bibr">32</xref>,<xref rid="R33" ref-type="bibr">33</xref></sup> (left panel). The significance of the clustering was evaluated by using SigClust34 with a p<0.0001. Fisher's exact test35 was used to check associations between the clusters and the histological subtypes (right panel). (<bold>b</bold>) Gene Set Enrichment Analysis (GSEA)<sup><xref rid="R21" ref-type="bibr">21</xref></sup> for SCLC versus PCA using RNAseq expression data. Low gene expression is indicated in blue and high expression, in red. On the right side are named the altered pathways in PCA (green) and SCLC (purple).</p></caption><graphic xlink:href="nihms-571151-f0003"></graphic></fig><table-wrap id="T1" position="float" orientation="portrait"><label>Table 1</label><caption><p>Overview of samples annotated for mutations in genes involved in histone methylation, and correspondent levels of H3K9me3 and H3K27me3 detected by immunohistochemistry.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="top" rowspan="1" colspan="1">SAMPLE</th><th align="center" valign="top" rowspan="1" colspan="1">MUTATION</th><th align="center" valign="top" rowspan="1" colspan="1">H3K9me3</th><th align="center" valign="top" rowspan="1" colspan="1">H3K27me3</th></tr></thead><tbody><tr><td align="center" valign="top" rowspan="1" colspan="1">S02333</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>JMJD1C</italic>_H954N</td><td align="center" valign="top" rowspan="1" colspan="1">Intermediate</td><td align="center" valign="top" rowspan="1" colspan="1">Low</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S01502</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>KDM4A</italic>_I168T</td><td align="center" valign="top" rowspan="1" colspan="1">Intermediate</td><td align="center" valign="top" rowspan="1" colspan="1">N/A</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S02323</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>MEN1</italic>_e3+1 and LOH</td><td align="center" valign="top" rowspan="1" colspan="1">Low</td><td align="center" valign="top" rowspan="1" colspan="1">Low</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S02339</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>NSD1</italic>_A1047G</td><td align="center" valign="top" rowspan="1" colspan="1">Intermediate</td><td align="center" valign="top" rowspan="1" colspan="1">Low</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S02327</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>CBX6</italic>_P302S and LOH</td><td align="center" valign="top" rowspan="1" colspan="1">Low</td><td align="center" valign="top" rowspan="1" colspan="1">Low</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S01746</td><td align="center" valign="top" rowspan="1" colspan="1"><italic>EZH1</italic>_R728G and LOH</td><td align="center" valign="top" rowspan="1" colspan="1">Low</td><td align="center" valign="top" rowspan="1" colspan="1">Intermediate</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S02325</td><td align="center" valign="top" rowspan="1" colspan="1">YY1_E253K</td><td align="center" valign="top" rowspan="1" colspan="1">Low</td><td align="center" valign="top" rowspan="1" colspan="1">Intermediate</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S01501</td><td align="center" valign="top" rowspan="1" colspan="1">Wild type</td><td align="center" valign="top" rowspan="1" colspan="1">N/A</td><td align="center" valign="top" rowspan="1" colspan="1">High</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S01731</td><td align="center" valign="top" rowspan="1" colspan="1">Wild type</td><td align="center" valign="top" rowspan="1" colspan="1">Low</td><td align="center" valign="top" rowspan="1" colspan="1">Low</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S01742</td><td align="center" valign="top" rowspan="1" colspan="1">Wild type</td><td align="center" valign="top" rowspan="1" colspan="1">High</td><td align="center" valign="top" rowspan="1" colspan="1">High</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S02334</td><td align="center" valign="top" rowspan="1" colspan="1">Wild type</td><td align="center" valign="top" rowspan="1" colspan="1">Intermediate</td><td align="center" valign="top" rowspan="1" colspan="1">High</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S02337</td><td align="center" valign="top" rowspan="1" colspan="1">Wild type</td><td align="center" valign="top" rowspan="1" colspan="1">High</td><td align="center" valign="top" rowspan="1" colspan="1">High</td></tr><tr><td align="center" valign="top" rowspan="1" colspan="1">S02338</td><td align="center" valign="top" rowspan="1" colspan="1">Wild type</td><td align="center" valign="top" rowspan="1" colspan="1">High</td><td align="center" valign="top" rowspan="1" colspan="1">Intermediate</td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Italie</li><li>Norvège</li><li>Royaume-Uni</li><li>Suisse</li><li>États-Unis</li></country><region><li>Berlin</li><li>District de Cologne</li><li>Rhénanie-du-Nord-Westphalie</li><li>Tennessee</li></region><settlement><li>Berlin</li><li>Bonn</li><li>Cologne</li></settlement></list><tree><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Fernandez Cuesta, Lynnette" sort="Fernandez Cuesta, Lynnette" uniqKey="Fernandez Cuesta L" first="Lynnette" last="Fernandez-Cuesta">Lynnette Fernandez-Cuesta</name></region><name sortKey="Achter, Viktor" sort="Achter, Viktor" uniqKey="Achter V" first="Viktor" last="Achter">Viktor Achter</name><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name><name sortKey="Ansen, Sascha" sort="Ansen, Sascha" uniqKey="Ansen S" first="Sascha" last="Ansén">Sascha Ansén</name><name sortKey="Bogus, Magdalena" sort="Bogus, Magdalena" uniqKey="Bogus M" first="Magdalena" last="Bogus">Magdalena Bogus</name><name sortKey="Bosco, Graziella" sort="Bosco, Graziella" uniqKey="Bosco G" first="Graziella" last="Bosco">Graziella Bosco</name><name sortKey="Buettner, Reinhard" sort="Buettner, Reinhard" uniqKey="Buettner R" first="Reinhard" last="Buettner">Reinhard Buettner</name><name sortKey="Buettner, Reinhard" sort="Buettner, Reinhard" uniqKey="Buettner R" first="Reinhard" last="Buettner">Reinhard Buettner</name><name sortKey="Buettner, Reinhard" sort="Buettner, Reinhard" uniqKey="Buettner R" first="Reinhard" last="Buettner">Reinhard Buettner</name><name sortKey="Dahmen, Ilona" sort="Dahmen, Ilona" uniqKey="Dahmen I" first="Ilona" last="Dahmen">Ilona Dahmen</name><name sortKey="George, Julie" sort="George, Julie" uniqKey="George J" first="Julie" last="George">Julie George</name><name sortKey="Haas, Stefan A" sort="Haas, Stefan A" uniqKey="Haas S" first="Stefan A." last="Haas">Stefan A. Haas</name><name sortKey="Heukamp, Lukas C" sort="Heukamp, Lukas C" uniqKey="Heukamp L" first="Lukas C" last="Heukamp">Lukas C. Heukamp</name><name sortKey="Heukamp, Lukas C" sort="Heukamp, Lukas C" uniqKey="Heukamp L" first="Lukas C" last="Heukamp">Lukas C. 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Thomas</name><name sortKey="Vingron, Martin" sort="Vingron, Martin" uniqKey="Vingron M" first="Martin" last="Vingron">Martin Vingron</name><name sortKey="Wolf, Jurgen" sort="Wolf, Jurgen" uniqKey="Wolf J" first="Jürgen" last="Wolf">Jürgen Wolf</name><name sortKey="Wolf, Jurgen" sort="Wolf, Jurgen" uniqKey="Wolf J" first="Jürgen" last="Wolf">Jürgen Wolf</name><name sortKey="Wolf, Jurgen" sort="Wolf, Jurgen" uniqKey="Wolf J" first="Jürgen" last="Wolf">Jürgen Wolf</name><name sortKey="Zander, Thomas" sort="Zander, Thomas" uniqKey="Zander T" first="Thomas" last="Zander">Thomas Zander</name><name sortKey="Zander, Thomas" sort="Zander, Thomas" uniqKey="Zander T" first="Thomas" last="Zander">Thomas Zander</name><name sortKey="Zander, Thomas" sort="Zander, Thomas" uniqKey="Zander T" first="Thomas" last="Zander">Thomas Zander</name></country><country name="Suisse"><noRegion><name sortKey="Soltermann, Alex" sort="Soltermann, Alex" uniqKey="Soltermann A" first="Alex" last="Soltermann">Alex Soltermann</name></noRegion></country><country name="Norvège"><noRegion><name sortKey="Brustugun, Odd Terje" sort="Brustugun, Odd Terje" uniqKey="Brustugun O" first="Odd Terje" last="Brustugun">Odd Terje Brustugun</name></noRegion><name sortKey="Brustugun, Odd Terje" sort="Brustugun, Odd Terje" uniqKey="Brustugun O" first="Odd Terje" last="Brustugun">Odd Terje Brustugun</name><name sortKey="Helland, Slaug" sort="Helland, Slaug" uniqKey="Helland " first=" Slaug" last="Helland"> Slaug Helland</name><name sortKey="Helland, Slaug" sort="Helland, Slaug" uniqKey="Helland " first=" Slaug" last="Helland"> Slaug Helland</name><name sortKey="Lund Iversen, Marius" sort="Lund Iversen, Marius" uniqKey="Lund Iversen M" first="Marius" last="Lund-Iversen">Marius Lund-Iversen</name><name sortKey="Solberg, Steinar" sort="Solberg, Steinar" uniqKey="Solberg S" first="Steinar" last="Solberg">Steinar Solberg</name></country><country name="Australie"><noRegion><name sortKey="Wright, Gavin M" sort="Wright, Gavin M" uniqKey="Wright G" first="Gavin M." last="Wright">Gavin M. Wright</name></noRegion><name sortKey="Russell, Prudence" sort="Russell, Prudence" uniqKey="Russell P" first="Prudence" last="Russell">Prudence Russell</name><name sortKey="Solomon, Benjamin" sort="Solomon, Benjamin" uniqKey="Solomon B" first="Benjamin" last="Solomon">Benjamin Solomon</name><name sortKey="Wainer, Zoe" sort="Wainer, Zoe" uniqKey="Wainer Z" first="Zoe" last="Wainer">Zoe Wainer</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Field, John K" sort="Field, John K" uniqKey="Field J" first="John K" last="Field">John K. Field</name></noRegion><name sortKey="Davies, Michael Pa" sort="Davies, Michael Pa" uniqKey="Davies M" first="Michael Pa." last="Davies">Michael Pa. Davies</name><name sortKey="Hyde, Russell" sort="Hyde, Russell" uniqKey="Hyde R" first="Russell" last="Hyde">Russell Hyde</name></country><country name="États-Unis"><region name="Tennessee"><name sortKey="Lovly, Christine" sort="Lovly, Christine" uniqKey="Lovly C" first="Christine" last="Lovly">Christine Lovly</name></region><name sortKey="Travis, William D" sort="Travis, William D" uniqKey="Travis W" first="William D" last="Travis">William D. Travis</name></country><country name="Italie"><noRegion><name sortKey="Cappuzzo, Federico" sort="Cappuzzo, Federico" uniqKey="Cappuzzo F" first="Federico" last="Cappuzzo">Federico Cappuzzo</name></noRegion></country><country name="France"><noRegion><name sortKey="Brambilla, Elisabeth" sort="Brambilla, Elisabeth" uniqKey="Brambilla E" first="Elisabeth" last="Brambilla">Elisabeth Brambilla</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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