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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Frequent and Focal <italic>FGFR1</italic> Amplification Associates With Therapeutically Tractable FGFR1 Dependency in Squamous-cell Lung Cancer</title><author><name sortKey="Weiss, Jonathan" sort="Weiss, Jonathan" uniqKey="Weiss J" first="Jonathan" last="Weiss">Jonathan Weiss</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Sos, Martin L" sort="Sos, Martin L" uniqKey="Sos M" first="Martin L." last="Sos">Martin L. Sos</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Seidel, Danila" sort="Seidel, Danila" uniqKey="Seidel D" first="Danila" last="Seidel">Danila Seidel</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Peifer, Martin" sort="Peifer, Martin" uniqKey="Peifer M" first="Martin" last="Peifer">Martin Peifer</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Zander, Thomas" sort="Zander, Thomas" uniqKey="Zander T" first="Thomas" last="Zander">Thomas Zander</name><affiliation><nlm:aff id="A3">Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Heuckmann, Johannes M" sort="Heuckmann, Johannes M" uniqKey="Heuckmann J" first="Johannes M." last="Heuckmann">Johannes M. Heuckmann</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Ullrich, Roland T" sort="Ullrich, Roland T" uniqKey="Ullrich R" first="Roland T." last="Ullrich">Roland T. Ullrich</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Menon, Roopika" sort="Menon, Roopika" uniqKey="Menon R" first="Roopika" last="Menon">Roopika Menon</name><affiliation><nlm:aff id="A4">Institute of Pathology, Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany</nlm:aff></affiliation></author><author><name sortKey="Maier, Sebastian" sort="Maier, Sebastian" uniqKey="Maier S" first="Sebastian" last="Maier">Sebastian Maier</name><affiliation><nlm:aff id="A4">Institute of Pathology, Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany</nlm:aff></affiliation></author><author><name sortKey="Soltermann, Alex" sort="Soltermann, Alex" uniqKey="Soltermann A" first="Alex" last="Soltermann">Alex Soltermann</name><affiliation><nlm:aff id="A5">Institute for Surgical Pathology, University Hospital Zurich, Zurich, Schweiz</nlm:aff></affiliation></author><author><name sortKey="Moch, Holger" sort="Moch, Holger" uniqKey="Moch H" first="Holger" last="Moch">Holger Moch</name><affiliation><nlm:aff id="A5">Institute for Surgical Pathology, University Hospital Zurich, Zurich, Schweiz</nlm:aff></affiliation></author><author><name sortKey="Wagener, Patrick" sort="Wagener, Patrick" uniqKey="Wagener P" first="Patrick" last="Wagener">Patrick Wagener</name><affiliation><nlm:aff id="A6">Department of Surgery, Weill Medical College of Cornell University, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Fischer, Florian" sort="Fischer, Florian" uniqKey="Fischer F" first="Florian" last="Fischer">Florian Fischer</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Heynck, Stefanie" sort="Heynck, Stefanie" uniqKey="Heynck S" first="Stefanie" last="Heynck">Stefanie Heynck</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Koker, Mirjam" sort="Koker, Mirjam" uniqKey="Koker M" first="Mirjam" last="Koker">Mirjam Koker</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Schottle, Jakob" sort="Schottle, Jakob" uniqKey="Schottle J" first="Jakob" last="Schöttle">Jakob Schöttle</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Leenders, Frauke" sort="Leenders, Frauke" uniqKey="Leenders F" first="Frauke" last="Leenders">Frauke Leenders</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Gabler, Franziska" sort="Gabler, Franziska" uniqKey="Gabler F" first="Franziska" last="Gabler">Franziska Gabler</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Dabow, Ines" sort="Dabow, Ines" uniqKey="Dabow I" first="Ines" last="Dabow">Ines Dabow</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Querings, Silvia" sort="Querings, Silvia" uniqKey="Querings S" first="Silvia" last="Querings">Silvia Querings</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></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><nlm:aff id="A7">Institute of Pathology, University of Bonn, Bonn, Germany</nlm:aff></affiliation></author><author><name sortKey="Balke Want, Hyatt" sort="Balke Want, Hyatt" uniqKey="Balke Want H" first="Hyatt" last="Balke-Want">Hyatt Balke-Want</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Ansen, Sascha" sort="Ansen, Sascha" uniqKey="Ansen S" first="Sascha" last="Ansén">Sascha Ansén</name><affiliation><nlm:aff id="A3">Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Rauh, Daniel" sort="Rauh, Daniel" uniqKey="Rauh D" first="Daniel" last="Rauh">Daniel Rauh</name><affiliation><nlm:aff id="A8">Chemical Genomics Center of the Max Planck Society, Dortmund, Germany</nlm:aff></affiliation></author><author><name sortKey="Baessmann, Ingelore" sort="Baessmann, Ingelore" uniqKey="Baessmann I" first="Ingelore" last="Baessmann">Ingelore Baessmann</name><affiliation><nlm:aff id="A9">Cologne Center for Genomics (CCG) and Institute for Genetics, University of Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name><affiliation><nlm:aff id="A9">Cologne Center for Genomics (CCG) and Institute for Genetics, University of Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Wainer, Zoe" sort="Wainer, Zoe" uniqKey="Wainer Z" first="Zoe" last="Wainer">Zoe Wainer</name><affiliation><nlm:aff id="A10">Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Conron, Matthew" sort="Conron, Matthew" uniqKey="Conron M" first="Matthew" last="Conron">Matthew Conron</name><affiliation><nlm:aff id="A10">Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Wright, Gavin" sort="Wright, Gavin" uniqKey="Wright G" first="Gavin" last="Wright">Gavin Wright</name><affiliation><nlm:aff id="A10">Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Russell, Prudence" sort="Russell, Prudence" uniqKey="Russell P" first="Prudence" last="Russell">Prudence Russell</name><affiliation><nlm:aff id="A11">Department of Pathology, StVincent's, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Solomon, Ben" sort="Solomon, Ben" uniqKey="Solomon B" first="Ben" last="Solomon">Ben Solomon</name><affiliation><nlm:aff id="A12">Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Brambilla, Elisabeth" sort="Brambilla, Elisabeth" uniqKey="Brambilla E" first="Elisabeth" last="Brambilla">Elisabeth Brambilla</name><affiliation><nlm:aff id="A13">Department of Pathology, Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Institut Albert Bonniot INSERM U823; Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation></author><author><name sortKey="Brambilla, Christian" sort="Brambilla, Christian" uniqKey="Brambilla C" first="Christian" last="Brambilla">Christian Brambilla</name><affiliation><nlm:aff id="A13">Department of Pathology, Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Institut Albert Bonniot INSERM U823; Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation></author><author><name sortKey="Lorimier, Philippe" sort="Lorimier, Philippe" uniqKey="Lorimier P" first="Philippe" last="Lorimier">Philippe Lorimier</name><affiliation><nlm:aff id="A13">Department of Pathology, Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation></author><author><name sortKey="Sollberg, Steinar" sort="Sollberg, Steinar" uniqKey="Sollberg S" first="Steinar" last="Sollberg">Steinar Sollberg</name><affiliation><nlm:aff id="A15">Deptartment of thoracic surgery, Rikshospitalet, Oslo University Hospital, Oslo Norway</nlm:aff></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><nlm:aff id="A16">Department of Radiation Biology, Norwegian Radium Hospital, Oslo, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Department of Oncology, Radiumhospitalet, Oslo University Hospital, Oslo, Norway</nlm:aff></affiliation></author><author><name sortKey="Engel Riedel, Walburga" sort="Engel Riedel, Walburga" uniqKey="Engel Riedel W" first="Walburga" last="Engel-Riedel">Walburga Engel-Riedel</name><affiliation><nlm:aff id="A18">Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Ludwig, Corinna" sort="Ludwig, Corinna" uniqKey="Ludwig C" first="Corinna" last="Ludwig">Corinna Ludwig</name><affiliation><nlm:aff id="A18">Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Petersen, Iver" sort="Petersen, Iver" uniqKey="Petersen I" first="Iver" last="Petersen">Iver Petersen</name><affiliation><nlm:aff id="A19">Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany</nlm:aff></affiliation></author><author><name sortKey="S Nger, Jorg" sort="S Nger, Jorg" uniqKey="S Nger J" first="Jörg" last="S Nger">Jörg S Nger</name><affiliation><nlm:aff id="A20">Institute for Pathology Bad Berka, Bad Berka, Germany</nlm:aff></affiliation></author><author><name sortKey="Clement, Joachim" sort="Clement, Joachim" uniqKey="Clement J" first="Joachim" last="Clement">Joachim Clement</name><affiliation><nlm:aff id="A21">Department for Internal Medicine II, University Clinic Jena, Friedrich-Schiller University, Jena, Germany</nlm:aff></affiliation></author><author><name sortKey="Groen, Harry" sort="Groen, Harry" uniqKey="Groen H" first="Harry" last="Groen">Harry Groen</name><affiliation><nlm:aff id="A22">Department of Pulmonary Diseases, University Medical Centre Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Timens, Wim" sort="Timens, Wim" uniqKey="Timens W" first="Wim" last="Timens">Wim Timens</name><affiliation><nlm:aff id="A23">Department of Pathology, University Medical Centre Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Sietsma, Hannie" sort="Sietsma, Hannie" uniqKey="Sietsma H" first="Hannie" last="Sietsma">Hannie Sietsma</name><affiliation><nlm:aff id="A23">Department of Pathology, University Medical Centre Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Thunnissen, Erik" sort="Thunnissen, Erik" uniqKey="Thunnissen E" first="Erik" last="Thunnissen">Erik Thunnissen</name><affiliation><nlm:aff id="A24">Department of Pathology, VU University medical center Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Smit, Egbert" sort="Smit, Egbert" uniqKey="Smit E" first="Egbert" last="Smit">Egbert Smit</name><affiliation><nlm:aff id="A25">Department of Pulmonary Diseases, VU University medical center Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Heideman, Danielle" sort="Heideman, Danielle" uniqKey="Heideman D" first="Daniëlle" last="Heideman">Daniëlle Heideman</name><affiliation><nlm:aff id="A24">Department of Pathology, VU University medical center Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Cappuzzo, Federico" sort="Cappuzzo, Federico" uniqKey="Cappuzzo F" first="Federico" last="Cappuzzo">Federico Cappuzzo</name><affiliation><nlm:aff id="A26">Department of medical oncology, Ospedale Civile, Livorno, Italy</nlm:aff></affiliation></author><author><name sortKey="Ligorio, Claudia" sort="Ligorio, Claudia" uniqKey="Ligorio C" first="Claudia" last="Ligorio">Claudia Ligorio</name><affiliation><nlm:aff id="A27">Department of Haematology and Oncologic Science, University Hospital Bologna, Bologna, Italy</nlm:aff></affiliation></author><author><name sortKey="Damiani, Stefania" sort="Damiani, Stefania" uniqKey="Damiani S" first="Stefania" last="Damiani">Stefania Damiani</name><affiliation><nlm:aff id="A27">Department of Haematology and Oncologic Science, University Hospital Bologna, Bologna, Italy</nlm:aff></affiliation></author><author><name sortKey="Hallek, Michael" sort="Hallek, Michael" uniqKey="Hallek M" first="Michael" last="Hallek">Michael Hallek</name><affiliation><nlm:aff id="A3">Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A32">Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Beroukhim, Rameen" sort="Beroukhim, Rameen" uniqKey="Beroukhim R" first="Rameen" last="Beroukhim">Rameen Beroukhim</name><affiliation><nlm:aff id="A28">Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Pao, William" sort="Pao, William" uniqKey="Pao W" first="William" last="Pao">William Pao</name><affiliation><nlm:aff id="A29">Vanderbilt-Ingram Cancer Center, Nashville, USA</nlm:aff></affiliation></author><author><name sortKey="Klebl, Bert" sort="Klebl, Bert" uniqKey="Klebl B" first="Bert" last="Klebl">Bert Klebl</name><affiliation><nlm:aff id="A30">Lead Discovery Center GmbH, Dortmund, Germany</nlm:aff></affiliation></author><author><name sortKey="Baumann, Matthias" sort="Baumann, Matthias" uniqKey="Baumann M" first="Matthias" last="Baumann">Matthias Baumann</name><affiliation><nlm:aff id="A30">Lead Discovery Center GmbH, Dortmund, Germany</nlm:aff></affiliation></author><author><name sortKey="Buettner, Reinhard" sort="Buettner, Reinhard" uniqKey="Buettner R" first="Reinhard" last="Buettner">Reinhard Buettner</name><affiliation><nlm:aff id="A7">Institute of Pathology, University of Bonn, Bonn, Germany</nlm:aff></affiliation></author><author><name sortKey="Ernestus, Karen" sort="Ernestus, Karen" uniqKey="Ernestus K" first="Karen" last="Ernestus">Karen Ernestus</name><affiliation><nlm:aff id="A31">Department of Pathology, Hospital Merheim, Kliniken der Stadt Köln gGmbH, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Stoelben, Erich" sort="Stoelben, Erich" uniqKey="Stoelben E" first="Erich" last="Stoelben">Erich Stoelben</name><affiliation><nlm:aff id="A18">Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Wolf, Jurgen" sort="Wolf, Jurgen" uniqKey="Wolf J" first="Jürgen" last="Wolf">Jürgen Wolf</name><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Nurnberg, Peter" sort="Nurnberg, Peter" uniqKey="Nurnberg P" first="Peter" last="Nürnberg">Peter Nürnberg</name><affiliation><nlm:aff id="A8">Chemical Genomics Center of the Max Planck Society, Dortmund, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A32">Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Perner, Sven" sort="Perner, Sven" uniqKey="Perner S" first="Sven" last="Perner">Sven Perner</name><affiliation><nlm:aff id="A4">Institute of Pathology, Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany</nlm:aff></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><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Institute of Pathology, University of Bonn, Bonn, Germany</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21160078</idno><idno type="pmc">3990281</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990281</idno><idno type="RBID">PMC:3990281</idno><idno type="doi">10.1126/scitranslmed.3001451</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">001E64</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E64</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Frequent and Focal <italic>FGFR1</italic> Amplification Associates With Therapeutically Tractable FGFR1 Dependency in Squamous-cell Lung Cancer</title><author><name sortKey="Weiss, Jonathan" sort="Weiss, Jonathan" uniqKey="Weiss J" first="Jonathan" last="Weiss">Jonathan Weiss</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Sos, Martin L" sort="Sos, Martin L" uniqKey="Sos M" first="Martin L." last="Sos">Martin L. Sos</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Seidel, Danila" sort="Seidel, Danila" uniqKey="Seidel D" first="Danila" last="Seidel">Danila Seidel</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Peifer, Martin" sort="Peifer, Martin" uniqKey="Peifer M" first="Martin" last="Peifer">Martin Peifer</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Zander, Thomas" sort="Zander, Thomas" uniqKey="Zander T" first="Thomas" last="Zander">Thomas Zander</name><affiliation><nlm:aff id="A3">Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Heuckmann, Johannes M" sort="Heuckmann, Johannes M" uniqKey="Heuckmann J" first="Johannes M." last="Heuckmann">Johannes M. Heuckmann</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Ullrich, Roland T" sort="Ullrich, Roland T" uniqKey="Ullrich R" first="Roland T." last="Ullrich">Roland T. Ullrich</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Menon, Roopika" sort="Menon, Roopika" uniqKey="Menon R" first="Roopika" last="Menon">Roopika Menon</name><affiliation><nlm:aff id="A4">Institute of Pathology, Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany</nlm:aff></affiliation></author><author><name sortKey="Maier, Sebastian" sort="Maier, Sebastian" uniqKey="Maier S" first="Sebastian" last="Maier">Sebastian Maier</name><affiliation><nlm:aff id="A4">Institute of Pathology, Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany</nlm:aff></affiliation></author><author><name sortKey="Soltermann, Alex" sort="Soltermann, Alex" uniqKey="Soltermann A" first="Alex" last="Soltermann">Alex Soltermann</name><affiliation><nlm:aff id="A5">Institute for Surgical Pathology, University Hospital Zurich, Zurich, Schweiz</nlm:aff></affiliation></author><author><name sortKey="Moch, Holger" sort="Moch, Holger" uniqKey="Moch H" first="Holger" last="Moch">Holger Moch</name><affiliation><nlm:aff id="A5">Institute for Surgical Pathology, University Hospital Zurich, Zurich, Schweiz</nlm:aff></affiliation></author><author><name sortKey="Wagener, Patrick" sort="Wagener, Patrick" uniqKey="Wagener P" first="Patrick" last="Wagener">Patrick Wagener</name><affiliation><nlm:aff id="A6">Department of Surgery, Weill Medical College of Cornell University, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Fischer, Florian" sort="Fischer, Florian" uniqKey="Fischer F" first="Florian" last="Fischer">Florian Fischer</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Heynck, Stefanie" sort="Heynck, Stefanie" uniqKey="Heynck S" first="Stefanie" last="Heynck">Stefanie Heynck</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Koker, Mirjam" sort="Koker, Mirjam" uniqKey="Koker M" first="Mirjam" last="Koker">Mirjam Koker</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Schottle, Jakob" sort="Schottle, Jakob" uniqKey="Schottle J" first="Jakob" last="Schöttle">Jakob Schöttle</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Leenders, Frauke" sort="Leenders, Frauke" uniqKey="Leenders F" first="Frauke" last="Leenders">Frauke Leenders</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Gabler, Franziska" sort="Gabler, Franziska" uniqKey="Gabler F" first="Franziska" last="Gabler">Franziska Gabler</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Dabow, Ines" sort="Dabow, Ines" uniqKey="Dabow I" first="Ines" last="Dabow">Ines Dabow</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Querings, Silvia" sort="Querings, Silvia" uniqKey="Querings S" first="Silvia" last="Querings">Silvia Querings</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></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><nlm:aff id="A7">Institute of Pathology, University of Bonn, Bonn, Germany</nlm:aff></affiliation></author><author><name sortKey="Balke Want, Hyatt" sort="Balke Want, Hyatt" uniqKey="Balke Want H" first="Hyatt" last="Balke-Want">Hyatt Balke-Want</name><affiliation><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Ansen, Sascha" sort="Ansen, Sascha" uniqKey="Ansen S" first="Sascha" last="Ansén">Sascha Ansén</name><affiliation><nlm:aff id="A3">Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Rauh, Daniel" sort="Rauh, Daniel" uniqKey="Rauh D" first="Daniel" last="Rauh">Daniel Rauh</name><affiliation><nlm:aff id="A8">Chemical Genomics Center of the Max Planck Society, Dortmund, Germany</nlm:aff></affiliation></author><author><name sortKey="Baessmann, Ingelore" sort="Baessmann, Ingelore" uniqKey="Baessmann I" first="Ingelore" last="Baessmann">Ingelore Baessmann</name><affiliation><nlm:aff id="A9">Cologne Center for Genomics (CCG) and Institute for Genetics, University of Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name><affiliation><nlm:aff id="A9">Cologne Center for Genomics (CCG) and Institute for Genetics, University of Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Wainer, Zoe" sort="Wainer, Zoe" uniqKey="Wainer Z" first="Zoe" last="Wainer">Zoe Wainer</name><affiliation><nlm:aff id="A10">Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Conron, Matthew" sort="Conron, Matthew" uniqKey="Conron M" first="Matthew" last="Conron">Matthew Conron</name><affiliation><nlm:aff id="A10">Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Wright, Gavin" sort="Wright, Gavin" uniqKey="Wright G" first="Gavin" last="Wright">Gavin Wright</name><affiliation><nlm:aff id="A10">Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Russell, Prudence" sort="Russell, Prudence" uniqKey="Russell P" first="Prudence" last="Russell">Prudence Russell</name><affiliation><nlm:aff id="A11">Department of Pathology, StVincent's, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Solomon, Ben" sort="Solomon, Ben" uniqKey="Solomon B" first="Ben" last="Solomon">Ben Solomon</name><affiliation><nlm:aff id="A12">Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Brambilla, Elisabeth" sort="Brambilla, Elisabeth" uniqKey="Brambilla E" first="Elisabeth" last="Brambilla">Elisabeth Brambilla</name><affiliation><nlm:aff id="A13">Department of Pathology, Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Institut Albert Bonniot INSERM U823; Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation></author><author><name sortKey="Brambilla, Christian" sort="Brambilla, Christian" uniqKey="Brambilla C" first="Christian" last="Brambilla">Christian Brambilla</name><affiliation><nlm:aff id="A13">Department of Pathology, Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Institut Albert Bonniot INSERM U823; Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation></author><author><name sortKey="Lorimier, Philippe" sort="Lorimier, Philippe" uniqKey="Lorimier P" first="Philippe" last="Lorimier">Philippe Lorimier</name><affiliation><nlm:aff id="A13">Department of Pathology, Université Joseph Fourier, Grenoble, France</nlm:aff></affiliation></author><author><name sortKey="Sollberg, Steinar" sort="Sollberg, Steinar" uniqKey="Sollberg S" first="Steinar" last="Sollberg">Steinar Sollberg</name><affiliation><nlm:aff id="A15">Deptartment of thoracic surgery, Rikshospitalet, Oslo University Hospital, Oslo Norway</nlm:aff></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><nlm:aff id="A16">Department of Radiation Biology, Norwegian Radium Hospital, Oslo, Norway</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Department of Oncology, Radiumhospitalet, Oslo University Hospital, Oslo, Norway</nlm:aff></affiliation></author><author><name sortKey="Engel Riedel, Walburga" sort="Engel Riedel, Walburga" uniqKey="Engel Riedel W" first="Walburga" last="Engel-Riedel">Walburga Engel-Riedel</name><affiliation><nlm:aff id="A18">Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Ludwig, Corinna" sort="Ludwig, Corinna" uniqKey="Ludwig C" first="Corinna" last="Ludwig">Corinna Ludwig</name><affiliation><nlm:aff id="A18">Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Petersen, Iver" sort="Petersen, Iver" uniqKey="Petersen I" first="Iver" last="Petersen">Iver Petersen</name><affiliation><nlm:aff id="A19">Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany</nlm:aff></affiliation></author><author><name sortKey="S Nger, Jorg" sort="S Nger, Jorg" uniqKey="S Nger J" first="Jörg" last="S Nger">Jörg S Nger</name><affiliation><nlm:aff id="A20">Institute for Pathology Bad Berka, Bad Berka, Germany</nlm:aff></affiliation></author><author><name sortKey="Clement, Joachim" sort="Clement, Joachim" uniqKey="Clement J" first="Joachim" last="Clement">Joachim Clement</name><affiliation><nlm:aff id="A21">Department for Internal Medicine II, University Clinic Jena, Friedrich-Schiller University, Jena, Germany</nlm:aff></affiliation></author><author><name sortKey="Groen, Harry" sort="Groen, Harry" uniqKey="Groen H" first="Harry" last="Groen">Harry Groen</name><affiliation><nlm:aff id="A22">Department of Pulmonary Diseases, University Medical Centre Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Timens, Wim" sort="Timens, Wim" uniqKey="Timens W" first="Wim" last="Timens">Wim Timens</name><affiliation><nlm:aff id="A23">Department of Pathology, University Medical Centre Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Sietsma, Hannie" sort="Sietsma, Hannie" uniqKey="Sietsma H" first="Hannie" last="Sietsma">Hannie Sietsma</name><affiliation><nlm:aff id="A23">Department of Pathology, University Medical Centre Groningen, Groningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Thunnissen, Erik" sort="Thunnissen, Erik" uniqKey="Thunnissen E" first="Erik" last="Thunnissen">Erik Thunnissen</name><affiliation><nlm:aff id="A24">Department of Pathology, VU University medical center Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Smit, Egbert" sort="Smit, Egbert" uniqKey="Smit E" first="Egbert" last="Smit">Egbert Smit</name><affiliation><nlm:aff id="A25">Department of Pulmonary Diseases, VU University medical center Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Heideman, Danielle" sort="Heideman, Danielle" uniqKey="Heideman D" first="Daniëlle" last="Heideman">Daniëlle Heideman</name><affiliation><nlm:aff id="A24">Department of Pathology, VU University medical center Amsterdam, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Cappuzzo, Federico" sort="Cappuzzo, Federico" uniqKey="Cappuzzo F" first="Federico" last="Cappuzzo">Federico Cappuzzo</name><affiliation><nlm:aff id="A26">Department of medical oncology, Ospedale Civile, Livorno, Italy</nlm:aff></affiliation></author><author><name sortKey="Ligorio, Claudia" sort="Ligorio, Claudia" uniqKey="Ligorio C" first="Claudia" last="Ligorio">Claudia Ligorio</name><affiliation><nlm:aff id="A27">Department of Haematology and Oncologic Science, University Hospital Bologna, Bologna, Italy</nlm:aff></affiliation></author><author><name sortKey="Damiani, Stefania" sort="Damiani, Stefania" uniqKey="Damiani S" first="Stefania" last="Damiani">Stefania Damiani</name><affiliation><nlm:aff id="A27">Department of Haematology and Oncologic Science, University Hospital Bologna, Bologna, Italy</nlm:aff></affiliation></author><author><name sortKey="Hallek, Michael" sort="Hallek, Michael" uniqKey="Hallek M" first="Michael" last="Hallek">Michael Hallek</name><affiliation><nlm:aff id="A3">Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A32">Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Beroukhim, Rameen" sort="Beroukhim, Rameen" uniqKey="Beroukhim R" first="Rameen" last="Beroukhim">Rameen Beroukhim</name><affiliation><nlm:aff id="A28">Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Pao, William" sort="Pao, William" uniqKey="Pao W" first="William" last="Pao">William Pao</name><affiliation><nlm:aff id="A29">Vanderbilt-Ingram Cancer Center, Nashville, USA</nlm:aff></affiliation></author><author><name sortKey="Klebl, Bert" sort="Klebl, Bert" uniqKey="Klebl B" first="Bert" last="Klebl">Bert Klebl</name><affiliation><nlm:aff id="A30">Lead Discovery Center GmbH, Dortmund, Germany</nlm:aff></affiliation></author><author><name sortKey="Baumann, Matthias" sort="Baumann, Matthias" uniqKey="Baumann M" first="Matthias" last="Baumann">Matthias Baumann</name><affiliation><nlm:aff id="A30">Lead Discovery Center GmbH, Dortmund, Germany</nlm:aff></affiliation></author><author><name sortKey="Buettner, Reinhard" sort="Buettner, Reinhard" uniqKey="Buettner R" first="Reinhard" last="Buettner">Reinhard Buettner</name><affiliation><nlm:aff id="A7">Institute of Pathology, University of Bonn, Bonn, Germany</nlm:aff></affiliation></author><author><name sortKey="Ernestus, Karen" sort="Ernestus, Karen" uniqKey="Ernestus K" first="Karen" last="Ernestus">Karen Ernestus</name><affiliation><nlm:aff id="A31">Department of Pathology, Hospital Merheim, Kliniken der Stadt Köln gGmbH, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Stoelben, Erich" sort="Stoelben, Erich" uniqKey="Stoelben E" first="Erich" last="Stoelben">Erich Stoelben</name><affiliation><nlm:aff id="A18">Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Wolf, Jurgen" sort="Wolf, Jurgen" uniqKey="Wolf J" first="Jürgen" last="Wolf">Jürgen Wolf</name><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Nurnberg, Peter" sort="Nurnberg, Peter" uniqKey="Nurnberg P" first="Peter" last="Nürnberg">Peter Nürnberg</name><affiliation><nlm:aff id="A8">Chemical Genomics Center of the Max Planck Society, Dortmund, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A32">Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Germany</nlm:aff></affiliation></author><author><name sortKey="Perner, Sven" sort="Perner, Sven" uniqKey="Perner S" first="Sven" last="Perner">Sven Perner</name><affiliation><nlm:aff id="A4">Institute of Pathology, Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany</nlm:aff></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><nlm:aff id="A1">Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Institute of Pathology, University of Bonn, Bonn, Germany</nlm:aff></affiliation></author></analytic><series><title level="j">Science translational medicine</title><idno type="ISSN">1946-6234</idno><idno type="eISSN">1946-6242</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2">Lung cancer remains one of the leading causes for cancer-related death in developed countries. In lung adenocarcinomas, <italic>EGFR</italic> mutations and <italic>EML4-ALK</italic> fusions are associated with response to EGFR and ALK inhibition. By contrast, therapeutically exploitable genetic alterations have been lacking in squamous-cell lung cancer. We conducted a systematic search for alterations that are therapeutically amenable and performed high-resolution gene-copy number analyses in a set of 232 lung cancer specimens. We identified frequent and focal <italic>FGFR1</italic> amplification in squamous-cell lung cancer (n=155), but not in other lung cancer subtypes, and confirmed its presence in an independent cohort of squamous-cell lung cancer samples employing FISH (22% of cases). Using cell-based screening with the FGFR inhibitor (PD173074) in a large (n=83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth (p=0.0002) and induced apoptosis (p=0.008) specifically in those lung cancer cells carrying amplified <italic>FGFR1</italic>. We validated the dependency on FGFR1 of <italic>FGFR1</italic>-amplified cell lines by knockdown of FGFR1 and by ectopic expression of a resistance allele of <italic>FGFR1</italic> (FGFR1<sup>V561M</sup>), which rescued <italic>FGFR1</italic>-amplified cells from PD173074-mediated cytotoxicity. Finally we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Focal <italic>FGFR1</italic> amplification is common in squamous-cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101505086</journal-id><journal-id journal-id-type="pubmed-jr-id">36963</journal-id><journal-id journal-id-type="nlm-ta">Sci Transl Med</journal-id><journal-id journal-id-type="iso-abbrev">Sci Transl Med</journal-id><journal-title-group><journal-title>Science translational medicine</journal-title></journal-title-group><issn pub-type="ppub">1946-6234</issn><issn pub-type="epub">1946-6242</issn></journal-meta><article-meta><article-id pub-id-type="pmid">21160078</article-id><article-id pub-id-type="pmc">3990281</article-id><article-id pub-id-type="doi">10.1126/scitranslmed.3001451</article-id><article-id pub-id-type="manuscript">NIHMS569992</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Frequent and Focal <italic>FGFR1</italic> Amplification Associates With Therapeutically Tractable FGFR1 Dependency in Squamous-cell Lung Cancer</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Weiss</surname><given-names>Jonathan</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sos</surname><given-names>Martin L.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Seidel</surname><given-names>Danila</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>Peifer</surname><given-names>Martin</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zander</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Heuckmann</surname><given-names>Johannes M.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ullrich</surname><given-names>Roland T.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Menon</surname><given-names>Roopika</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Maier</surname><given-names>Sebastian</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Soltermann</surname><given-names>Alex</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Moch</surname><given-names>Holger</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Wagener</surname><given-names>Patrick</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Fischer</surname><given-names>Florian</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Heynck</surname><given-names>Stefanie</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Koker</surname><given-names>Mirjam</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Schöttle</surname><given-names>Jakob</given-names></name><xref ref-type="aff" rid="A1">1</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="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Gabler</surname><given-names>Franziska</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>Dabow</surname><given-names>Ines</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>Querings</surname><given-names>Silvia</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Heukamp</surname><given-names>Lukas C.</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Balke-Want</surname><given-names>Hyatt</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ansén</surname><given-names>Sascha</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Rauh</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib 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contrib-type="author"><name><surname>Baumann</surname><given-names>Matthias</given-names></name><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Buettner</surname><given-names>Reinhard</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Ernestus</surname><given-names>Karen</given-names></name><xref ref-type="aff" rid="A31">31</xref></contrib><contrib contrib-type="author"><name><surname>Stoelben</surname><given-names>Erich</given-names></name><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Wolf</surname><given-names>Jürgen</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Nürnberg</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A32">32</xref></contrib><contrib contrib-type="author"><name><surname>Perner</surname><given-names>Sven</given-names></name><xref ref-type="aff" rid="A4">4</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="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A7">7</xref></contrib></contrib-group><aff id="A1"><label>1</label>Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany</aff><aff id="A2"><label>2</label>Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</aff><aff id="A3"><label>3</label>Department I of Internal Medicine and Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany</aff><aff id="A4"><label>4</label>Institute of Pathology, Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany</aff><aff id="A5"><label>5</label>Institute for Surgical Pathology, University Hospital Zurich, Zurich, Schweiz</aff><aff id="A6"><label>6</label>Department of Surgery, Weill Medical College of Cornell University, New York, USA</aff><aff id="A7"><label>7</label>Institute of Pathology, University of Bonn, Bonn, Germany</aff><aff id="A8"><label>8</label>Chemical Genomics Center of the Max Planck Society, Dortmund, Germany</aff><aff id="A9"><label>9</label>Cologne Center for Genomics (CCG) and Institute for Genetics, University of Cologne, Germany</aff><aff id="A10"><label>10</label>Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia</aff><aff id="A11"><label>11</label>Department of Pathology, StVincent's, Melbourne, Australia</aff><aff id="A12"><label>12</label>Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia</aff><aff id="A13"><label>13</label>Department of Pathology, Université Joseph Fourier, Grenoble, France</aff><aff id="A14"><label>14</label>Institut Albert Bonniot INSERM U823; Université Joseph Fourier, Grenoble, France</aff><aff id="A15"><label>15</label>Deptartment of thoracic surgery, Rikshospitalet, Oslo University Hospital, Oslo Norway</aff><aff id="A16"><label>16</label>Department of Radiation Biology, Norwegian Radium Hospital, Oslo, Norway</aff><aff id="A17"><label>17</label>Department of Oncology, Radiumhospitalet, Oslo University Hospital, Oslo, Norway</aff><aff id="A18"><label>18</label>Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, Cologne, Germany</aff><aff id="A19"><label>19</label>Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany</aff><aff id="A20"><label>20</label>Institute for Pathology Bad Berka, Bad Berka, Germany</aff><aff id="A21"><label>21</label>Department for Internal Medicine II, University Clinic Jena, Friedrich-Schiller University, Jena, Germany</aff><aff id="A22"><label>22</label>Department of Pulmonary Diseases, University Medical Centre Groningen, Groningen, The Netherlands</aff><aff id="A23"><label>23</label>Department of Pathology, University Medical Centre Groningen, Groningen, The Netherlands</aff><aff id="A24"><label>24</label>Department of Pathology, VU University medical center Amsterdam, Amsterdam, The Netherlands</aff><aff id="A25"><label>25</label>Department of Pulmonary Diseases, VU University medical center Amsterdam, Amsterdam, The Netherlands</aff><aff id="A26"><label>26</label>Department of medical oncology, Ospedale Civile, Livorno, Italy</aff><aff id="A27"><label>27</label>Department of Haematology and Oncologic Science, University Hospital Bologna, Bologna, Italy</aff><aff id="A28"><label>28</label>Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA</aff><aff id="A29"><label>29</label>Vanderbilt-Ingram Cancer Center, Nashville, USA</aff><aff id="A30"><label>30</label>Lead Discovery Center GmbH, Dortmund, Germany</aff><aff id="A31"><label>31</label>Department of Pathology, Hospital Merheim, Kliniken der Stadt Köln gGmbH, Cologne, Germany</aff><aff id="A32"><label>32</label>Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Germany</aff><author-notes><corresp id="cor1">Correspondence: <bold>Martin L. Sos</bold>, <email>martin.sos@nf.mpg.de</email>; Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, 50931 Cologne, Germany, Tel.: +49-221-4726287, Fax.: +49-221-4726-298, <bold>Roman K. Thomas</bold>, <email>nini@nf.mpg.de</email>, Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, 50931 Cologne, Germany, Tel.: +49-221-4726259, Fax.: +49-221-4726-298</corresp><fn id="FN1" fn-type="equal"><p id="P1">JW, MLS and DS contributed equally to this project</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>10</day><month>4</month><year>2014</year></pub-date><pub-date pub-type="ppub"><day>15</day><month>12</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>17</day><month>4</month><year>2014</year></pub-date><volume>2</volume><issue>62</issue><fpage>62ra93</fpage><lpage>62ra93</lpage><pmc-comment>elocation-id from pubmed: 10.1126/scitranslmed.3001451</pmc-comment>
<abstract><p id="P2">Lung cancer remains one of the leading causes for cancer-related death in developed countries. In lung adenocarcinomas, <italic>EGFR</italic> mutations and <italic>EML4-ALK</italic> fusions are associated with response to EGFR and ALK inhibition. By contrast, therapeutically exploitable genetic alterations have been lacking in squamous-cell lung cancer. We conducted a systematic search for alterations that are therapeutically amenable and performed high-resolution gene-copy number analyses in a set of 232 lung cancer specimens. We identified frequent and focal <italic>FGFR1</italic> amplification in squamous-cell lung cancer (n=155), but not in other lung cancer subtypes, and confirmed its presence in an independent cohort of squamous-cell lung cancer samples employing FISH (22% of cases). Using cell-based screening with the FGFR inhibitor (PD173074) in a large (n=83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth (p=0.0002) and induced apoptosis (p=0.008) specifically in those lung cancer cells carrying amplified <italic>FGFR1</italic>. We validated the dependency on FGFR1 of <italic>FGFR1</italic>-amplified cell lines by knockdown of FGFR1 and by ectopic expression of a resistance allele of <italic>FGFR1</italic> (FGFR1<sup>V561M</sup>), which rescued <italic>FGFR1</italic>-amplified cells from PD173074-mediated cytotoxicity. Finally we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Focal <italic>FGFR1</italic> amplification is common in squamous-cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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