CD74-NRG1 fusions in lung adenocarcinoma.
Identifieur interne : 003B61 ( Main/Exploration ); précédent : 003B60; suivant : 003B62CD74-NRG1 fusions in lung adenocarcinoma.
Auteurs : Lynnette Fernandez-Cuesta [Belgique] ; Dennis Plenker ; Hirotaka Osada ; Ruping Sun ; Roopika Menon ; Frauke Leenders ; Sandra Ortiz-Cuaran ; Martin Peifer ; Marc Bos ; Juliane Da Ler ; Florian Malchers ; Jakob Schöttle ; Wenzel Vogel ; Ilona Dahmen ; Mirjam Koker ; Roland T. Ullrich ; Gavin M. Wright ; Prudence A. Russell ; Zoe Wainer ; Benjamin Solomon ; Elisabeth Brambilla ; Hélène Nagy-Mignotte ; Denis Moro-Sibilot ; Christian G. Brambilla ; Sylvie Lantuejoul ; Janine Altmüller ; Christian Becker ; Peter Nürnberg ; Johannes M. Heuckmann ; Erich Stoelben ; Iver Petersen ; Joachim H. Clement ; Jörg S Nger ; Lucia A. Muscarella ; Annamaria La Torre ; Vito M. Fazio ; Idoya Lahortiga ; Timothy Perera ; Souichi Ogata ; Marc Parade ; Dirk Brehmer ; Martin Vingron ; Lukas C. Heukamp ; Reinhard Buettner ; Thomas Zander ; Jürgen Wolf ; Sven Perner ; Sascha Ansén ; Stefan A. Haas ; Yasushi Yatabe ; Roman K. ThomasSource :
- Cancer discovery [ 2159-8290 ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Adénocarcinome (anatomopathologie), Adénocarcinome (génétique), Adénocarcinome mucineux (anatomopathologie), Adénocarcinome mucineux (génétique), Analyse de profil d'expression de gènes, Analyse de séquence d'ADN, Animaux, Antigènes d'histocompatibilité de classe II (génétique), Antigènes de différenciation des lymphocytes B (génétique), Cellules NIH 3T3, Données de séquences moléculaires, Femelle, Humains, Lignée cellulaire tumorale, Mâle, Neuréguline-1 (génétique), Protéines de fusion oncogènes (génétique), Protéines de fusion oncogènes (métabolisme), Souris, Sujet âgé, Sujet âgé de 80 ans ou plus, Séquence nucléotidique, Transduction du signal (génétique), Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (génétique).
- MESH :
- anatomopathologie : Adénocarcinome, Adénocarcinome mucineux, Tumeurs du poumon.
- génétique : Adénocarcinome, Adénocarcinome mucineux, Antigènes d'histocompatibilité de classe II, Antigènes de différenciation des lymphocytes B, Neuréguline-1, Protéines de fusion oncogènes, Transduction du signal, Tumeurs du poumon.
- métabolisme : Protéines de fusion oncogènes.
- Adulte, Adulte d'âge moyen, Analyse de profil d'expression de gènes, Analyse de séquence d'ADN, Animaux, Cellules NIH 3T3, Données de séquences moléculaires, Femelle, Humains, Lignée cellulaire tumorale, Mâle, Souris, Sujet âgé, Sujet âgé de 80 ans ou plus, Séquence nucléotidique.
English descriptors
- KwdEn :
- Adenocarcinoma (genetics), Adenocarcinoma (pathology), Adenocarcinoma, Mucinous (genetics), Adenocarcinoma, Mucinous (pathology), Adult, Aged, Aged, 80 and over, Animals, Antigens, Differentiation, B-Lymphocyte (genetics), Base Sequence, Cell Line, Tumor, Female, Gene Expression Profiling, Histocompatibility Antigens Class II (genetics), Humans, Lung Neoplasms (genetics), Lung Neoplasms (pathology), Male, Mice, Middle Aged, Molecular Sequence Data, NIH 3T3 Cells, Neuregulin-1 (genetics), Oncogene Proteins, Fusion (genetics), Oncogene Proteins, Fusion (metabolism), Sequence Analysis, DNA, Signal Transduction (genetics).
- MESH :
- chemical , genetics : Antigens, Differentiation, B-Lymphocyte, Histocompatibility Antigens Class II, Neuregulin-1, Oncogene Proteins, Fusion.
- genetics : Adenocarcinoma, Adenocarcinoma, Mucinous, Lung Neoplasms, Signal Transduction.
- chemical , metabolism : Oncogene Proteins, Fusion.
- pathology : Adenocarcinoma, Adenocarcinoma, Mucinous, Lung Neoplasms.
- Adult, Aged, Aged, 80 and over, Animals, Base Sequence, Cell Line, Tumor, Female, Gene Expression Profiling, Humans, Male, Mice, Middle Aged, Molecular Sequence Data, NIH 3T3 Cells, Sequence Analysis, DNA.
Abstract
We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations, we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-β3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case, and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (P < 0.0001). Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment.
DOI: 10.1158/2159-8290.CD-13-0633
PubMed: 24469108
Affiliations:
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Le document en format XML
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<author><name sortKey="Fernandez Cuesta, Lynnette" sort="Fernandez Cuesta, Lynnette" uniqKey="Fernandez Cuesta L" first="Lynnette" last="Fernandez-Cuesta">Lynnette Fernandez-Cuesta</name>
<affiliation wicri:level="1"><nlm:affiliation>1Department of Translational Genomics; 2Department I of Internal Medicine; 3Laboratory of Translational Cancer Genomics; 4Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne-Bonn; 5Center for Molecular Medicine Cologne (CMMC); 6Cologne Center for Genomics (CCG); 7Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD); 8Department of Pathology, University Hospital Medical Center, University of Cologne; 9Blackfield AG; 10Max Planck Institute for Neurological Research; 11Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH; 12Institute of Human Genetics, Cologne; 13Computational Molecular Biology Department, Max Planck Institute for Molecular Genetics, Berlin; 14Department of Prostate Cancer Research, Institute of Pathology; 15Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn; 16Institute of Pathology; 17Department of Internal Medicine II, Jena University Hospital, Friedrich-Schiller-University, Jena; 18Institute for Pathology Bad Berka, Bad Berka, Germany;19Division of Molecular Oncology, Aichi Cancer Center Research Institute; 20Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan; Departments of 21Surgery and22Pathology, St. Vincent's Hospital; 23Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia;24Department of Pathology, 25CHU Grenoble Institut National de la Santé et de la Recherche Medicale (INSERM) U823, Institute Albert Bonniot, Grenoble-Alpes University, Grenoble, France; 26Laboratory of Oncology IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo; 27Laboratory for Molecular Medicine and Biotechnology, University Campus Bio-Medico, Rome, Italy; 28Center for the Biology of Disease, VIB, Leuven; and 29Oncology Discovery, Janssen Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>1Department of Translational Genomics; 2Department I of Internal Medicine; 3Laboratory of Translational Cancer Genomics; 4Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne-Bonn; 5Center for Molecular Medicine Cologne (CMMC); 6Cologne Center for Genomics (CCG); 7Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD); 8Department of Pathology, University Hospital Medical Center, University of Cologne; 9Blackfield AG; 10Max Planck Institute for Neurological Research; 11Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH; 12Institute of Human Genetics, Cologne; 13Computational Molecular Biology Department, Max Planck Institute for Molecular Genetics, Berlin; 14Department of Prostate Cancer Research, Institute of Pathology; 15Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn; 16Institute of Pathology; 17Department of Internal Medicine II, Jena University Hospital, Friedrich-Schiller-University, Jena; 18Institute for Pathology Bad Berka, Bad Berka, Germany;19Division of Molecular Oncology, Aichi Cancer Center Research Institute; 20Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan; Departments of 21Surgery and22Pathology, St. Vincent's Hospital; 23Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia;24Department of Pathology, 25CHU Grenoble Institut National de la Santé et de la Recherche Medicale (INSERM) U823, Institute Albert Bonniot, Grenoble-Alpes University, Grenoble, France; 26Laboratory of Oncology IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo; 27Laboratory for Molecular Medicine and Biotechnology, University Campus Bio-Medico, Rome, Italy; 28Center for the Biology of Disease, VIB, Leuven; and 29Oncology Discovery, Janssen Research and Development, A Division of Janssen Pharmaceutica NV, Beerse</wicri:regionArea>
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<author><name sortKey="Ortiz Cuaran, Sandra" sort="Ortiz Cuaran, Sandra" uniqKey="Ortiz Cuaran S" first="Sandra" last="Ortiz-Cuaran">Sandra Ortiz-Cuaran</name>
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<author><name sortKey="Nagy Mignotte, Helene" sort="Nagy Mignotte, Helene" uniqKey="Nagy Mignotte H" first="Hélène" last="Nagy-Mignotte">Hélène Nagy-Mignotte</name>
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<author><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name>
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<author><name sortKey="Becker, Christian" sort="Becker, Christian" uniqKey="Becker C" first="Christian" last="Becker">Christian Becker</name>
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<author><name sortKey="Muscarella, Lucia A" sort="Muscarella, Lucia A" uniqKey="Muscarella L" first="Lucia A" last="Muscarella">Lucia A. Muscarella</name>
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<author><name sortKey="La Torre, Annamaria" sort="La Torre, Annamaria" uniqKey="La Torre A" first="Annamaria" last="La Torre">Annamaria La Torre</name>
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<author><name sortKey="Fazio, Vito M" sort="Fazio, Vito M" uniqKey="Fazio V" first="Vito M" last="Fazio">Vito M. Fazio</name>
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<author><name sortKey="Lahortiga, Idoya" sort="Lahortiga, Idoya" uniqKey="Lahortiga I" first="Idoya" last="Lahortiga">Idoya Lahortiga</name>
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<author><name sortKey="Perera, Timothy" sort="Perera, Timothy" uniqKey="Perera T" first="Timothy" last="Perera">Timothy Perera</name>
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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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<author><name sortKey="Thomas, Roman K" sort="Thomas, Roman K" uniqKey="Thomas R" first="Roman K" last="Thomas">Roman K. Thomas</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">CD74-NRG1 fusions in lung adenocarcinoma.</title>
<author><name sortKey="Fernandez Cuesta, Lynnette" sort="Fernandez Cuesta, Lynnette" uniqKey="Fernandez Cuesta L" first="Lynnette" last="Fernandez-Cuesta">Lynnette Fernandez-Cuesta</name>
<affiliation wicri:level="1"><nlm:affiliation>1Department of Translational Genomics; 2Department I of Internal Medicine; 3Laboratory of Translational Cancer Genomics; 4Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne-Bonn; 5Center for Molecular Medicine Cologne (CMMC); 6Cologne Center for Genomics (CCG); 7Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD); 8Department of Pathology, University Hospital Medical Center, University of Cologne; 9Blackfield AG; 10Max Planck Institute for Neurological Research; 11Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH; 12Institute of Human Genetics, Cologne; 13Computational Molecular Biology Department, Max Planck Institute for Molecular Genetics, Berlin; 14Department of Prostate Cancer Research, Institute of Pathology; 15Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn; 16Institute of Pathology; 17Department of Internal Medicine II, Jena University Hospital, Friedrich-Schiller-University, Jena; 18Institute for Pathology Bad Berka, Bad Berka, Germany;19Division of Molecular Oncology, Aichi Cancer Center Research Institute; 20Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan; Departments of 21Surgery and22Pathology, St. Vincent's Hospital; 23Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia;24Department of Pathology, 25CHU Grenoble Institut National de la Santé et de la Recherche Medicale (INSERM) U823, Institute Albert Bonniot, Grenoble-Alpes University, Grenoble, France; 26Laboratory of Oncology IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo; 27Laboratory for Molecular Medicine and Biotechnology, University Campus Bio-Medico, Rome, Italy; 28Center for the Biology of Disease, VIB, Leuven; and 29Oncology Discovery, Janssen Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>1Department of Translational Genomics; 2Department I of Internal Medicine; 3Laboratory of Translational Cancer Genomics; 4Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne-Bonn; 5Center for Molecular Medicine Cologne (CMMC); 6Cologne Center for Genomics (CCG); 7Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD); 8Department of Pathology, University Hospital Medical Center, University of Cologne; 9Blackfield AG; 10Max Planck Institute for Neurological Research; 11Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH; 12Institute of Human Genetics, Cologne; 13Computational Molecular Biology Department, Max Planck Institute for Molecular Genetics, Berlin; 14Department of Prostate Cancer Research, Institute of Pathology; 15Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn; 16Institute of Pathology; 17Department of Internal Medicine II, Jena University Hospital, Friedrich-Schiller-University, Jena; 18Institute for Pathology Bad Berka, Bad Berka, Germany;19Division of Molecular Oncology, Aichi Cancer Center Research Institute; 20Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan; Departments of 21Surgery and22Pathology, St. Vincent's Hospital; 23Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia;24Department of Pathology, 25CHU Grenoble Institut National de la Santé et de la Recherche Medicale (INSERM) U823, Institute Albert Bonniot, Grenoble-Alpes University, Grenoble, France; 26Laboratory of Oncology IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo; 27Laboratory for Molecular Medicine and Biotechnology, University Campus Bio-Medico, Rome, Italy; 28Center for the Biology of Disease, VIB, Leuven; and 29Oncology Discovery, Janssen Research and Development, A Division of Janssen Pharmaceutica NV, Beerse</wicri:regionArea>
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<author><name sortKey="Plenker, Dennis" sort="Plenker, Dennis" uniqKey="Plenker D" first="Dennis" last="Plenker">Dennis Plenker</name>
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<author><name sortKey="Osada, Hirotaka" sort="Osada, Hirotaka" uniqKey="Osada H" first="Hirotaka" last="Osada">Hirotaka Osada</name>
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<author><name sortKey="Sun, Ruping" sort="Sun, Ruping" uniqKey="Sun R" first="Ruping" last="Sun">Ruping Sun</name>
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<author><name sortKey="Leenders, Frauke" sort="Leenders, Frauke" uniqKey="Leenders F" first="Frauke" last="Leenders">Frauke Leenders</name>
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<author><name sortKey="Ortiz Cuaran, Sandra" sort="Ortiz Cuaran, Sandra" uniqKey="Ortiz Cuaran S" first="Sandra" last="Ortiz-Cuaran">Sandra Ortiz-Cuaran</name>
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<author><name sortKey="Peifer, Martin" sort="Peifer, Martin" uniqKey="Peifer M" first="Martin" last="Peifer">Martin Peifer</name>
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<author><name sortKey="Bos, Marc" sort="Bos, Marc" uniqKey="Bos M" first="Marc" last="Bos">Marc Bos</name>
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<author><name sortKey="Da Ler, Juliane" sort="Da Ler, Juliane" uniqKey="Da Ler J" first="Juliane" last="Da Ler">Juliane Da Ler</name>
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<author><name sortKey="Malchers, Florian" sort="Malchers, Florian" uniqKey="Malchers F" first="Florian" last="Malchers">Florian Malchers</name>
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<author><name sortKey="Schottle, Jakob" sort="Schottle, Jakob" uniqKey="Schottle J" first="Jakob" last="Schöttle">Jakob Schöttle</name>
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<author><name sortKey="Vogel, Wenzel" sort="Vogel, Wenzel" uniqKey="Vogel W" first="Wenzel" last="Vogel">Wenzel Vogel</name>
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<author><name sortKey="Dahmen, Ilona" sort="Dahmen, Ilona" uniqKey="Dahmen I" first="Ilona" last="Dahmen">Ilona Dahmen</name>
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<author><name sortKey="Koker, Mirjam" sort="Koker, Mirjam" uniqKey="Koker M" first="Mirjam" last="Koker">Mirjam Koker</name>
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<author><name sortKey="Ullrich, Roland T" sort="Ullrich, Roland T" uniqKey="Ullrich R" first="Roland T" last="Ullrich">Roland T. Ullrich</name>
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<author><name sortKey="Wright, Gavin M" sort="Wright, Gavin M" uniqKey="Wright G" first="Gavin M" last="Wright">Gavin M. Wright</name>
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<author><name sortKey="Russell, Prudence A" sort="Russell, Prudence A" uniqKey="Russell P" first="Prudence A" last="Russell">Prudence A. Russell</name>
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<author><name sortKey="Wainer, Zoe" sort="Wainer, Zoe" uniqKey="Wainer Z" first="Zoe" last="Wainer">Zoe Wainer</name>
</author>
<author><name sortKey="Solomon, Benjamin" sort="Solomon, Benjamin" uniqKey="Solomon B" first="Benjamin" last="Solomon">Benjamin Solomon</name>
</author>
<author><name sortKey="Brambilla, Elisabeth" sort="Brambilla, Elisabeth" uniqKey="Brambilla E" first="Elisabeth" last="Brambilla">Elisabeth Brambilla</name>
</author>
<author><name sortKey="Nagy Mignotte, Helene" sort="Nagy Mignotte, Helene" uniqKey="Nagy Mignotte H" first="Hélène" last="Nagy-Mignotte">Hélène Nagy-Mignotte</name>
</author>
<author><name sortKey="Moro Sibilot, Denis" sort="Moro Sibilot, Denis" uniqKey="Moro Sibilot D" first="Denis" last="Moro-Sibilot">Denis Moro-Sibilot</name>
</author>
<author><name sortKey="Brambilla, Christian G" sort="Brambilla, Christian G" uniqKey="Brambilla C" first="Christian G" last="Brambilla">Christian G. Brambilla</name>
</author>
<author><name sortKey="Lantuejoul, Sylvie" sort="Lantuejoul, Sylvie" uniqKey="Lantuejoul S" first="Sylvie" last="Lantuejoul">Sylvie Lantuejoul</name>
</author>
<author><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name>
</author>
<author><name sortKey="Becker, Christian" sort="Becker, Christian" uniqKey="Becker C" first="Christian" last="Becker">Christian Becker</name>
</author>
<author><name sortKey="Nurnberg, Peter" sort="Nurnberg, Peter" uniqKey="Nurnberg P" first="Peter" last="Nürnberg">Peter Nürnberg</name>
</author>
<author><name sortKey="Heuckmann, Johannes M" sort="Heuckmann, Johannes M" uniqKey="Heuckmann J" first="Johannes M" last="Heuckmann">Johannes M. Heuckmann</name>
</author>
<author><name sortKey="Stoelben, Erich" sort="Stoelben, Erich" uniqKey="Stoelben E" first="Erich" last="Stoelben">Erich Stoelben</name>
</author>
<author><name sortKey="Petersen, Iver" sort="Petersen, Iver" uniqKey="Petersen I" first="Iver" last="Petersen">Iver Petersen</name>
</author>
<author><name sortKey="Clement, Joachim H" sort="Clement, Joachim H" uniqKey="Clement J" first="Joachim H" last="Clement">Joachim H. Clement</name>
</author>
<author><name sortKey="S Nger, Jorg" sort="S Nger, Jorg" uniqKey="S Nger J" first="Jörg" last="S Nger">Jörg S Nger</name>
</author>
<author><name sortKey="Muscarella, Lucia A" sort="Muscarella, Lucia A" uniqKey="Muscarella L" first="Lucia A" last="Muscarella">Lucia A. Muscarella</name>
</author>
<author><name sortKey="La Torre, Annamaria" sort="La Torre, Annamaria" uniqKey="La Torre A" first="Annamaria" last="La Torre">Annamaria La Torre</name>
</author>
<author><name sortKey="Fazio, Vito M" sort="Fazio, Vito M" uniqKey="Fazio V" first="Vito M" last="Fazio">Vito M. Fazio</name>
</author>
<author><name sortKey="Lahortiga, Idoya" sort="Lahortiga, Idoya" uniqKey="Lahortiga I" first="Idoya" last="Lahortiga">Idoya Lahortiga</name>
</author>
<author><name sortKey="Perera, Timothy" sort="Perera, Timothy" uniqKey="Perera T" first="Timothy" last="Perera">Timothy Perera</name>
</author>
<author><name sortKey="Ogata, Souichi" sort="Ogata, Souichi" uniqKey="Ogata S" first="Souichi" last="Ogata">Souichi Ogata</name>
</author>
<author><name sortKey="Parade, Marc" sort="Parade, Marc" uniqKey="Parade M" first="Marc" last="Parade">Marc Parade</name>
</author>
<author><name sortKey="Brehmer, Dirk" sort="Brehmer, Dirk" uniqKey="Brehmer D" first="Dirk" last="Brehmer">Dirk Brehmer</name>
</author>
<author><name sortKey="Vingron, Martin" sort="Vingron, Martin" uniqKey="Vingron M" first="Martin" last="Vingron">Martin Vingron</name>
</author>
<author><name sortKey="Heukamp, Lukas C" sort="Heukamp, Lukas C" uniqKey="Heukamp L" first="Lukas C" last="Heukamp">Lukas C. Heukamp</name>
</author>
<author><name sortKey="Buettner, Reinhard" sort="Buettner, Reinhard" uniqKey="Buettner R" first="Reinhard" last="Buettner">Reinhard Buettner</name>
</author>
<author><name sortKey="Zander, Thomas" sort="Zander, Thomas" uniqKey="Zander T" first="Thomas" last="Zander">Thomas Zander</name>
</author>
<author><name sortKey="Wolf, Jurgen" sort="Wolf, Jurgen" uniqKey="Wolf J" first="Jürgen" last="Wolf">Jürgen Wolf</name>
</author>
<author><name sortKey="Perner, Sven" sort="Perner, Sven" uniqKey="Perner S" first="Sven" last="Perner">Sven Perner</name>
</author>
<author><name sortKey="Ansen, Sascha" sort="Ansen, Sascha" uniqKey="Ansen S" first="Sascha" last="Ansén">Sascha Ansén</name>
</author>
<author><name sortKey="Haas, Stefan A" sort="Haas, Stefan A" uniqKey="Haas S" first="Stefan A" last="Haas">Stefan A. Haas</name>
</author>
<author><name sortKey="Yatabe, Yasushi" sort="Yatabe, Yasushi" uniqKey="Yatabe Y" first="Yasushi" last="Yatabe">Yasushi Yatabe</name>
</author>
<author><name sortKey="Thomas, Roman K" sort="Thomas, Roman K" uniqKey="Thomas R" first="Roman K" last="Thomas">Roman K. Thomas</name>
</author>
</analytic>
<series><title level="j">Cancer discovery</title>
<idno type="eISSN">2159-8290</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenocarcinoma (genetics)</term>
<term>Adenocarcinoma (pathology)</term>
<term>Adenocarcinoma, Mucinous (genetics)</term>
<term>Adenocarcinoma, Mucinous (pathology)</term>
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Animals</term>
<term>Antigens, Differentiation, B-Lymphocyte (genetics)</term>
<term>Base Sequence</term>
<term>Cell Line, Tumor</term>
<term>Female</term>
<term>Gene Expression Profiling</term>
<term>Histocompatibility Antigens Class II (genetics)</term>
<term>Humans</term>
<term>Lung Neoplasms (genetics)</term>
<term>Lung Neoplasms (pathology)</term>
<term>Male</term>
<term>Mice</term>
<term>Middle Aged</term>
<term>Molecular Sequence Data</term>
<term>NIH 3T3 Cells</term>
<term>Neuregulin-1 (genetics)</term>
<term>Oncogene Proteins, Fusion (genetics)</term>
<term>Oncogene Proteins, Fusion (metabolism)</term>
<term>Sequence Analysis, DNA</term>
<term>Signal Transduction (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Adénocarcinome (anatomopathologie)</term>
<term>Adénocarcinome (génétique)</term>
<term>Adénocarcinome mucineux (anatomopathologie)</term>
<term>Adénocarcinome mucineux (génétique)</term>
<term>Analyse de profil d'expression de gènes</term>
<term>Analyse de séquence d'ADN</term>
<term>Animaux</term>
<term>Antigènes d'histocompatibilité de classe II (génétique)</term>
<term>Antigènes de différenciation des lymphocytes B (génétique)</term>
<term>Cellules NIH 3T3</term>
<term>Données de séquences moléculaires</term>
<term>Femelle</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Mâle</term>
<term>Neuréguline-1 (génétique)</term>
<term>Protéines de fusion oncogènes (génétique)</term>
<term>Protéines de fusion oncogènes (métabolisme)</term>
<term>Souris</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Séquence nucléotidique</term>
<term>Transduction du signal (génétique)</term>
<term>Tumeurs du poumon (anatomopathologie)</term>
<term>Tumeurs du poumon (génétique)</term>
</keywords>
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<term>Histocompatibility Antigens Class II</term>
<term>Neuregulin-1</term>
<term>Oncogene Proteins, Fusion</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Adénocarcinome</term>
<term>Adénocarcinome mucineux</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Adenocarcinoma</term>
<term>Adenocarcinoma, Mucinous</term>
<term>Lung Neoplasms</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Adénocarcinome</term>
<term>Adénocarcinome mucineux</term>
<term>Antigènes d'histocompatibilité de classe II</term>
<term>Antigènes de différenciation des lymphocytes B</term>
<term>Neuréguline-1</term>
<term>Protéines de fusion oncogènes</term>
<term>Transduction du signal</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Oncogene Proteins, Fusion</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines de fusion oncogènes</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Adenocarcinoma</term>
<term>Adenocarcinoma, Mucinous</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Animals</term>
<term>Base Sequence</term>
<term>Cell Line, Tumor</term>
<term>Female</term>
<term>Gene Expression Profiling</term>
<term>Humans</term>
<term>Male</term>
<term>Mice</term>
<term>Middle Aged</term>
<term>Molecular Sequence Data</term>
<term>NIH 3T3 Cells</term>
<term>Sequence Analysis, DNA</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><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>Animaux</term>
<term>Cellules NIH 3T3</term>
<term>Données de séquences moléculaires</term>
<term>Femelle</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Mâle</term>
<term>Souris</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Séquence nucléotidique</term>
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<front><div type="abstract" xml:lang="en">We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations, we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-β3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case, and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (P < 0.0001). Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment.</div>
</front>
</TEI>
<affiliations><list><country><li>Belgique</li>
</country>
</list>
<tree><noCountry><name sortKey="Altmuller, Janine" sort="Altmuller, Janine" uniqKey="Altmuller J" first="Janine" last="Altmüller">Janine Altmüller</name>
<name sortKey="Ansen, Sascha" sort="Ansen, Sascha" uniqKey="Ansen S" first="Sascha" last="Ansén">Sascha Ansén</name>
<name sortKey="Becker, Christian" sort="Becker, Christian" uniqKey="Becker C" first="Christian" last="Becker">Christian Becker</name>
<name sortKey="Bos, Marc" sort="Bos, Marc" uniqKey="Bos M" first="Marc" last="Bos">Marc Bos</name>
<name sortKey="Brambilla, Christian G" sort="Brambilla, Christian G" uniqKey="Brambilla C" first="Christian G" last="Brambilla">Christian G. Brambilla</name>
<name sortKey="Brambilla, Elisabeth" sort="Brambilla, Elisabeth" uniqKey="Brambilla E" first="Elisabeth" last="Brambilla">Elisabeth Brambilla</name>
<name sortKey="Brehmer, Dirk" sort="Brehmer, Dirk" uniqKey="Brehmer D" first="Dirk" last="Brehmer">Dirk Brehmer</name>
<name sortKey="Buettner, Reinhard" sort="Buettner, Reinhard" uniqKey="Buettner R" first="Reinhard" last="Buettner">Reinhard Buettner</name>
<name sortKey="Clement, Joachim H" sort="Clement, Joachim H" uniqKey="Clement J" first="Joachim H" last="Clement">Joachim H. Clement</name>
<name sortKey="Da Ler, Juliane" sort="Da Ler, Juliane" uniqKey="Da Ler J" first="Juliane" last="Da Ler">Juliane Da Ler</name>
<name sortKey="Dahmen, Ilona" sort="Dahmen, Ilona" uniqKey="Dahmen I" first="Ilona" last="Dahmen">Ilona Dahmen</name>
<name sortKey="Fazio, Vito M" sort="Fazio, Vito M" uniqKey="Fazio V" first="Vito M" last="Fazio">Vito M. Fazio</name>
<name sortKey="Haas, Stefan A" sort="Haas, Stefan A" uniqKey="Haas S" first="Stefan A" last="Haas">Stefan A. Haas</name>
<name sortKey="Heuckmann, Johannes M" sort="Heuckmann, Johannes M" uniqKey="Heuckmann J" first="Johannes M" last="Heuckmann">Johannes M. Heuckmann</name>
<name sortKey="Heukamp, Lukas C" sort="Heukamp, Lukas C" uniqKey="Heukamp L" first="Lukas C" last="Heukamp">Lukas C. Heukamp</name>
<name sortKey="Koker, Mirjam" sort="Koker, Mirjam" uniqKey="Koker M" first="Mirjam" last="Koker">Mirjam Koker</name>
<name sortKey="La Torre, Annamaria" sort="La Torre, Annamaria" uniqKey="La Torre A" first="Annamaria" last="La Torre">Annamaria La Torre</name>
<name sortKey="Lahortiga, Idoya" sort="Lahortiga, Idoya" uniqKey="Lahortiga I" first="Idoya" last="Lahortiga">Idoya Lahortiga</name>
<name sortKey="Lantuejoul, Sylvie" sort="Lantuejoul, Sylvie" uniqKey="Lantuejoul S" first="Sylvie" last="Lantuejoul">Sylvie Lantuejoul</name>
<name sortKey="Leenders, Frauke" sort="Leenders, Frauke" uniqKey="Leenders F" first="Frauke" last="Leenders">Frauke Leenders</name>
<name sortKey="Malchers, Florian" sort="Malchers, Florian" uniqKey="Malchers F" first="Florian" last="Malchers">Florian Malchers</name>
<name sortKey="Menon, Roopika" sort="Menon, Roopika" uniqKey="Menon R" first="Roopika" last="Menon">Roopika Menon</name>
<name sortKey="Moro Sibilot, Denis" sort="Moro Sibilot, Denis" uniqKey="Moro Sibilot D" first="Denis" last="Moro-Sibilot">Denis Moro-Sibilot</name>
<name sortKey="Muscarella, Lucia A" sort="Muscarella, Lucia A" uniqKey="Muscarella L" first="Lucia A" last="Muscarella">Lucia A. Muscarella</name>
<name sortKey="Nagy Mignotte, Helene" sort="Nagy Mignotte, Helene" uniqKey="Nagy Mignotte H" first="Hélène" last="Nagy-Mignotte">Hélène Nagy-Mignotte</name>
<name sortKey="Nurnberg, Peter" sort="Nurnberg, Peter" uniqKey="Nurnberg P" first="Peter" last="Nürnberg">Peter Nürnberg</name>
<name sortKey="Ogata, Souichi" sort="Ogata, Souichi" uniqKey="Ogata S" first="Souichi" last="Ogata">Souichi Ogata</name>
<name sortKey="Ortiz Cuaran, Sandra" sort="Ortiz Cuaran, Sandra" uniqKey="Ortiz Cuaran S" first="Sandra" last="Ortiz-Cuaran">Sandra Ortiz-Cuaran</name>
<name sortKey="Osada, Hirotaka" sort="Osada, Hirotaka" uniqKey="Osada H" first="Hirotaka" last="Osada">Hirotaka Osada</name>
<name sortKey="Parade, Marc" sort="Parade, Marc" uniqKey="Parade M" first="Marc" last="Parade">Marc Parade</name>
<name sortKey="Peifer, Martin" sort="Peifer, Martin" uniqKey="Peifer M" first="Martin" last="Peifer">Martin Peifer</name>
<name sortKey="Perera, Timothy" sort="Perera, Timothy" uniqKey="Perera T" first="Timothy" last="Perera">Timothy Perera</name>
<name sortKey="Perner, Sven" sort="Perner, Sven" uniqKey="Perner S" first="Sven" last="Perner">Sven Perner</name>
<name sortKey="Petersen, Iver" sort="Petersen, Iver" uniqKey="Petersen I" first="Iver" last="Petersen">Iver Petersen</name>
<name sortKey="Plenker, Dennis" sort="Plenker, Dennis" uniqKey="Plenker D" first="Dennis" last="Plenker">Dennis Plenker</name>
<name sortKey="Russell, Prudence A" sort="Russell, Prudence A" uniqKey="Russell P" first="Prudence A" last="Russell">Prudence A. Russell</name>
<name sortKey="S Nger, Jorg" sort="S Nger, Jorg" uniqKey="S Nger J" first="Jörg" last="S Nger">Jörg S Nger</name>
<name sortKey="Schottle, Jakob" sort="Schottle, Jakob" uniqKey="Schottle J" first="Jakob" last="Schöttle">Jakob Schöttle</name>
<name sortKey="Solomon, Benjamin" sort="Solomon, Benjamin" uniqKey="Solomon B" first="Benjamin" last="Solomon">Benjamin Solomon</name>
<name sortKey="Stoelben, Erich" sort="Stoelben, Erich" uniqKey="Stoelben E" first="Erich" last="Stoelben">Erich Stoelben</name>
<name sortKey="Sun, Ruping" sort="Sun, Ruping" uniqKey="Sun R" first="Ruping" last="Sun">Ruping Sun</name>
<name sortKey="Thomas, Roman K" sort="Thomas, Roman K" uniqKey="Thomas R" first="Roman K" last="Thomas">Roman K. Thomas</name>
<name sortKey="Ullrich, Roland T" sort="Ullrich, Roland T" uniqKey="Ullrich R" first="Roland T" last="Ullrich">Roland T. Ullrich</name>
<name sortKey="Vingron, Martin" sort="Vingron, Martin" uniqKey="Vingron M" first="Martin" last="Vingron">Martin Vingron</name>
<name sortKey="Vogel, Wenzel" sort="Vogel, Wenzel" uniqKey="Vogel W" first="Wenzel" last="Vogel">Wenzel Vogel</name>
<name sortKey="Wainer, Zoe" sort="Wainer, Zoe" uniqKey="Wainer Z" first="Zoe" last="Wainer">Zoe Wainer</name>
<name sortKey="Wolf, Jurgen" sort="Wolf, Jurgen" uniqKey="Wolf J" first="Jürgen" last="Wolf">Jürgen Wolf</name>
<name sortKey="Wright, Gavin M" sort="Wright, Gavin M" uniqKey="Wright G" first="Gavin M" last="Wright">Gavin M. Wright</name>
<name sortKey="Yatabe, Yasushi" sort="Yatabe, Yasushi" uniqKey="Yatabe Y" first="Yasushi" last="Yatabe">Yasushi Yatabe</name>
<name sortKey="Zander, Thomas" sort="Zander, Thomas" uniqKey="Zander T" first="Thomas" last="Zander">Thomas Zander</name>
</noCountry>
<country name="Belgique"><noRegion><name sortKey="Fernandez Cuesta, Lynnette" sort="Fernandez Cuesta, Lynnette" uniqKey="Fernandez Cuesta L" first="Lynnette" last="Fernandez-Cuesta">Lynnette Fernandez-Cuesta</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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