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Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids

Identifieur interne : 003936 ( Main/Exploration ); précédent : 003935; suivant : 003937

Frequent 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 :

RBID : PMC:4132974

Descripteurs français

English descriptors

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 MEN1, PSIP1 and ARID1A being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine tumors, TP53 and RB1 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.


Url:
DOI: 10.1038/ncomms4518
PubMed: 24670920
PubMed Central: 4132974


Affiliations:


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Le document en format XML

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<wicri:regionArea>Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, University of Cologne, 50924 Cologne</wicri:regionArea>
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<name sortKey="George, Julie" sort="George, Julie" uniqKey="George J" first="Julie" last="George">Julie George</name>
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<name sortKey="Dahmen, Ilona" sort="Dahmen, Ilona" uniqKey="Dahmen I" first="Ilona" last="Dahmen">Ilona Dahmen</name>
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<name sortKey="Pinther, Berit" sort="Pinther, Berit" uniqKey="Pinther B" first="Berit" last="Pinther">Berit Pinther</name>
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<name sortKey="Bosco, Graziella" sort="Bosco, Graziella" uniqKey="Bosco G" first="Graziella" last="Bosco">Graziella Bosco</name>
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<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>
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<name sortKey="Konrad, Kathryn" sort="Konrad, Kathryn" uniqKey="Konrad K" first="Kathryn" last="Konrad">Kathryn Konrad</name>
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<name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name>
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<wicri:regionArea>Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne</wicri:regionArea>
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<wicri:noRegion>Cologne</wicri:noRegion>
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<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>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
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<name sortKey="Nurnberg, Peter" sort="Nurnberg, Peter" uniqKey="Nurnberg P" first="Peter" last="Nürnberg">Peter Nürnberg</name>
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<wicri:regionArea>Cologne Center for Genomics (CCG), University of Cologne, Cologne</wicri:regionArea>
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<name sortKey="Achter, Viktor" sort="Achter, Viktor" uniqKey="Achter V" first="Viktor" last="Achter">Viktor Achter</name>
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<country xml:lang="fr">Allemagne</country>
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<author>
<name sortKey="Lang, Ulrich" sort="Lang, Ulrich" uniqKey="Lang U" first="Ulrich" last="Lang">Ulrich Lang</name>
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<nlm:aff id="A11">Computing Center, University of Cologne, 50931 Cologne, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
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<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>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
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<name sortKey="Schneider, Peter M" sort="Schneider, Peter M" uniqKey="Schneider P" first="Peter M" last="Schneider">Peter M. Schneider</name>
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<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>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Cologne</settlement>
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<author>
<name sortKey="Bogus, Magdalena" sort="Bogus, Magdalena" uniqKey="Bogus M" first="Magdalena" last="Bogus">Magdalena Bogus</name>
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<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>
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<author>
<name sortKey="Soltermann, Alex" sort="Soltermann, Alex" uniqKey="Soltermann A" first="Alex" last="Soltermann">Alex Soltermann</name>
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<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>
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</affiliation>
</author>
<author>
<name sortKey="Brustugun, Odd Terje" sort="Brustugun, Odd Terje" uniqKey="Brustugun O" first="Odd Terje" last="Brustugun">Odd Terje Brustugun</name>
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<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>
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</affiliation>
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<name sortKey="Helland, Slaug" sort="Helland, Slaug" uniqKey="Helland " first=" Slaug" last="Helland"> Slaug Helland</name>
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<name sortKey="Solberg, Steinar" sort="Solberg, Steinar" uniqKey="Solberg S" first="Steinar" last="Solberg">Steinar Solberg</name>
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<name sortKey="Lund Iversen, Marius" sort="Lund Iversen, Marius" uniqKey="Lund Iversen M" first="Marius" last="Lund-Iversen">Marius Lund-Iversen</name>
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<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>
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<author>
<name sortKey="Ansen, Sascha" sort="Ansen, Sascha" uniqKey="Ansen S" first="Sascha" last="Ansén">Sascha Ansén</name>
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<name sortKey="Russell, Prudence" sort="Russell, Prudence" uniqKey="Russell P" first="Prudence" last="Russell">Prudence Russell</name>
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<nlm:aff id="A21">Department of Pathology, St. Vincent’s Hospital, Melbourne, 3065 Victoria, Australia</nlm:aff>
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<wicri:regionArea>Department of Pathology, St. Vincent’s Hospital, Melbourne, 3065 Victoria</wicri:regionArea>
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<name sortKey="Wainer, Zoe" sort="Wainer, Zoe" uniqKey="Wainer Z" first="Zoe" last="Wainer">Zoe Wainer</name>
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<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>
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<name sortKey="Hyde, Russell" sort="Hyde, Russell" uniqKey="Hyde R" first="Russell" last="Hyde">Russell Hyde</name>
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<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>
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<name sortKey="Davies, Michael Pa" sort="Davies, Michael Pa" uniqKey="Davies M" first="Michael Pa." last="Davies">Michael Pa. Davies</name>
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<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>
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<name sortKey="Heukamp, Lukas C" sort="Heukamp, Lukas C" uniqKey="Heukamp L" first="Lukas C" last="Heukamp">Lukas C. Heukamp</name>
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<country xml:lang="fr">Allemagne</country>
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<name sortKey="Petersen, Iver" sort="Petersen, Iver" uniqKey="Petersen I" first="Iver" last="Petersen">Iver Petersen</name>
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<nlm:aff id="A24">Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, 07743 Jena, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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<wicri:noRegion>07743 Jena</wicri:noRegion>
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<name sortKey="Perner, Sven" sort="Perner, Sven" uniqKey="Perner S" first="Sven" last="Perner">Sven Perner</name>
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<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>
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<name sortKey="Lovly, Christine" sort="Lovly, Christine" uniqKey="Lovly C" first="Christine" last="Lovly">Christine Lovly</name>
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<nlm:aff id="A26">Vanderbilt-Ingram Cancer Center, Nashville, TN37232, USA</nlm:aff>
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<region type="state">Tennessee</region>
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<name sortKey="Cappuzzo, Federico" sort="Cappuzzo, Federico" uniqKey="Cappuzzo F" first="Federico" last="Cappuzzo">Federico Cappuzzo</name>
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<name sortKey="Travis, William D" sort="Travis, William D" uniqKey="Travis W" first="William D" last="Travis">William D. Travis</name>
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<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>
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<name sortKey="Wolf, Jurgen" sort="Wolf, Jurgen" uniqKey="Wolf J" first="Jürgen" last="Wolf">Jürgen Wolf</name>
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<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>
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<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>
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<name sortKey="Vingron, Martin" sort="Vingron, Martin" uniqKey="Vingron M" first="Martin" last="Vingron">Martin Vingron</name>
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<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>
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<name sortKey="Brambilla, Elisabeth" sort="Brambilla, Elisabeth" uniqKey="Brambilla E" first="Elisabeth" last="Brambilla">Elisabeth Brambilla</name>
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<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>
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<name sortKey="Haas, Stefan A" sort="Haas, Stefan A" uniqKey="Haas S" first="Stefan A." last="Haas">Stefan A. Haas</name>
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<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>
<keywords scheme="KwdEn" xml:lang="en">
<term>Adolescent</term>
<term>Adult</term>
<term>Aged</term>
<term>Base Sequence</term>
<term>Carcinoid Tumor (genetics)</term>
<term>Carcinoid Tumor (pathology)</term>
<term>Chromatin Assembly and Disassembly (genetics)</term>
<term>Chromosome Mapping</term>
<term>DNA Copy Number Variations</term>
<term>Exome (genetics)</term>
<term>Female</term>
<term>Gene Dosage</term>
<term>Gene Expression Profiling</term>
<term>Gene Expression Regulation, Neoplastic</term>
<term>Genome, Human (genetics)</term>
<term>Humans</term>
<term>Lung Neoplasms (genetics)</term>
<term>Lung Neoplasms (pathology)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Molecular Sequence Data</term>
<term>Mutation</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Sequence Analysis, DNA</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de profil d'expression de gènes</term>
<term>Analyse de séquence d'ADN</term>
<term>Assemblage et désassemblage de la chromatine (génétique)</term>
<term>Cartographie chromosomique</term>
<term>Données de séquences moléculaires</term>
<term>Dosage génique</term>
<term>Exome (génétique)</term>
<term>Femelle</term>
<term>Génome humain (génétique)</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Mutation</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Régulation de l'expression des gènes tumoraux</term>
<term>Sujet âgé</term>
<term>Séquence nucléotidique</term>
<term>Tumeur carcinoïde (anatomopathologie)</term>
<term>Tumeur carcinoïde (génétique)</term>
<term>Tumeurs du poumon (anatomopathologie)</term>
<term>Tumeurs du poumon (génétique)</term>
<term>Variations de nombre de copies de segment d'ADN</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Tumeur carcinoïde</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Carcinoid Tumor</term>
<term>Chromatin Assembly and Disassembly</term>
<term>Exome</term>
<term>Genome, Human</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Assemblage et désassemblage de la chromatine</term>
<term>Exome</term>
<term>Génome humain</term>
<term>Tumeur carcinoïde</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Carcinoid Tumor</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adolescent</term>
<term>Adult</term>
<term>Aged</term>
<term>Base Sequence</term>
<term>Chromosome Mapping</term>
<term>DNA Copy Number Variations</term>
<term>Female</term>
<term>Gene Dosage</term>
<term>Gene Expression Profiling</term>
<term>Gene Expression Regulation, Neoplastic</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Molecular Sequence Data</term>
<term>Mutation</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Sequence Analysis, DNA</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de profil d'expression de gènes</term>
<term>Analyse de séquence d'ADN</term>
<term>Cartographie chromosomique</term>
<term>Données de séquences moléculaires</term>
<term>Dosage génique</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Mutation</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Régulation de l'expression des gènes tumoraux</term>
<term>Sujet âgé</term>
<term>Séquence nucléotidique</term>
<term>Variations de nombre de copies de segment d'ADN</term>
</keywords>
</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. These data also suggest that inactivation of chromatin remodeling genes is sufficient to drive transformation in pulmonary carcinoids.</p>
</div>
</front>
<back>
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<name sortKey="Subramanian, A" uniqKey="Subramanian A">A Subramanian</name>
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<name sortKey="Muhlemann, O" uniqKey="Muhlemann O">O Muhlemann</name>
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<name sortKey="Timp, W" uniqKey="Timp W">W Timp</name>
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<analytic>
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<name sortKey="Li, H" uniqKey="Li H">H Li</name>
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<name sortKey="Durbin, R" uniqKey="Durbin R">R Durbin</name>
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</analytic>
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<analytic>
<author>
<name sortKey="Lawrence, Ms" uniqKey="Lawrence M">MS Lawrence</name>
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<analytic>
<author>
<name sortKey="Benjamini, Y" uniqKey="Benjamini Y">Y Benjamini</name>
</author>
<author>
<name sortKey="Hochberg, Y" uniqKey="Hochberg Y">Y Hochberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Black, Jc" uniqKey="Black J">JC Black</name>
</author>
<author>
<name sortKey="Van Rechem, C" uniqKey="Van Rechem C">C Van Rechem</name>
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<name sortKey="Whetstine, Jr" uniqKey="Whetstine J">JR Whetstine</name>
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</analytic>
</biblStruct>
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<author>
<name sortKey="Olshen, Ab" uniqKey="Olshen A">AB Olshen</name>
</author>
<author>
<name sortKey="Venkatraman, Es" uniqKey="Venkatraman E">ES Venkatraman</name>
</author>
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</author>
<author>
<name sortKey="Wigler, M" uniqKey="Wigler M">M Wigler</name>
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</analytic>
</biblStruct>
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<analytic>
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<name sortKey="Wu, Td" uniqKey="Wu T">TD Wu</name>
</author>
<author>
<name sortKey="Nacu, S" uniqKey="Nacu S">S Nacu</name>
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<analytic>
<author>
<name sortKey="Kuehn, H" uniqKey="Kuehn H">H Kuehn</name>
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<author>
<name sortKey="Liberzon, A" uniqKey="Liberzon A">A Liberzon</name>
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</author>
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<name sortKey="Mesirov, Jp" uniqKey="Mesirov J">JP Mesirov</name>
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</analytic>
</biblStruct>
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<analytic>
<author>
<name sortKey="Wilkerson, Md" uniqKey="Wilkerson M">MD Wilkerson</name>
</author>
<author>
<name sortKey="Hayes, Dn" uniqKey="Hayes D">DN Hayes</name>
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</analytic>
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<analytic>
<author>
<name sortKey="Monti, S" uniqKey="Monti S">S Monti</name>
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<biblStruct>
<analytic>
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<name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name>
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<author>
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<analytic>
<author>
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<li>Suisse</li>
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<name sortKey="Wainer, Zoe" sort="Wainer, Zoe" uniqKey="Wainer Z" first="Zoe" last="Wainer">Zoe Wainer</name>
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