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Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids.
Fernandez-Cuesta, Lynnette; Peifer, Martin; Lu, Xin; Sun, Ruping; Ozretic, Luka; Seidal, Danila; Zander, Thomas; Leenders, Frauke; George, Julie; Müller, Christian; Dahmen, Ilona; Pinther, Berit; Bosco, Graziella; Konrad, Kathryn; Altmüller, Janine; Nürnberg, Peter; Achter, Viktor; Lang, Ulrich; Schneider, Peter M; Bogus, Magdalena; Soltermann, Alex; Brustugun, Odd Terje; Helland, Åslaug; Solberg, Steinar; Lund-Iversen, Marius; Ansén, Sascha; Stoelben, Erich; Wright, Gavin M; Russell, Prudence; Wainer, Zoe; Solomon, Benjamin; Field, John K; Hyde, Russell; Davies, Michael Pa; Heukamp, Lukas C; Petersen, Iver; Perner, Sven; Lovly, Christine; Cappuzzo, Federico; Travis, William D; Wolf, Jürgen; Vingron, Martin; Brambilla, Elisabeth; Haas, Stefan A; Buettner, Reinhard; Thomas, Roman K.
Afiliación
  • Fernandez-Cuesta L; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Peifer M; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Lu X; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Sun R; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Ozretic L; Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany.
  • Seidal D; Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany.
  • Zander T; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Leenders F; Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne - Bonn, University of Cologne, 50924 Cologne, Germany.
  • George J; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Müller C; Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Dahmen I; Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany.
  • Pinther B; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Bosco G; Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne - Bonn, University of Cologne, 50924 Cologne, Germany.
  • Konrad K; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Altmüller J; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Nürnberg P; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Achter V; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Lang U; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Schneider PM; Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany.
  • Bogus M; Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany.
  • Soltermann A; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Brustugun OT; Institute of Human Genetics, University of Cologne, Cologne 50931, Germany.
  • Helland Å; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
  • Solberg S; Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany.
  • Lund-Iversen M; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Ansén S; Computing Center, University of Cologne, 50931 Cologne, Germany.
  • Stoelben E; Computing Center, University of Cologne, 50931 Cologne, Germany.
  • Wright GM; Department of Informatics, University of Cologne, 50931 Cologne, Germany.
  • Russell P; Institute of Legal Medicine, University of Cologne, 50823 Cologne, Germany.
  • Wainer Z; Institute of Legal Medicine, University of Cologne, 50823 Cologne, Germany.
  • Solomon B; Institute for Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland.
  • Field JK; Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway.
  • Hyde R; Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway.
  • Davies MP; Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway.
  • Heukamp LC; Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway.
  • Petersen I; Department of Thoracic Surgery, Rikshospitalet, Oslo University Hospital, N-0027 Oslo, Norway.
  • Perner S; Department of pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway.
  • Lovly C; Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne, Germany.
  • Cappuzzo F; Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, 51109 Cologne, Germany.
  • Travis WD; University of Melbourne Department of Surgery, St Vincent's Hospital, Melbourne, 3065 Victoria, Australia.
  • Wolf J; Department of Pathology, St. Vincent's Hospital, Melbourne, 3065 Victoria, Australia.
  • Vingron M; University of Melbourne Department of Surgery, St Vincent's Hospital, Melbourne, 3065 Victoria, Australia.
  • Brambilla E; Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, 3002 Victoria, Australia.
  • Haas SA; 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.
  • Buettner R; 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.
  • Thomas RK; 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.
Nat Commun ; 5: 3518, 2014 Mar 27.
Article en En | MEDLINE | ID: mdl-24670920
ABSTRACT
Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours have not been systematically studied so far. Here we perform gene copy number analysis (n=54), genome/exome (n=44) and transcriptome (n=69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodelling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40 and 22.2% of the cases, respectively, with MEN1, PSIP1 and ARID1A being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine lung tumours, TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumours but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatin-remodelling genes is sufficient to drive transformation in pulmonary carcinoids.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tumor Carcinoide / Ensamble y Desensamble de Cromatina / Neoplasias Pulmonares / Mutación Límite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2014 Tipo del documento: Article País de afiliación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tumor Carcinoide / Ensamble y Desensamble de Cromatina / Neoplasias Pulmonares / Mutación Límite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2014 Tipo del documento: Article País de afiliación: Alemania