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Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling.
Forget, Antoine; Martignetti, Loredana; Puget, Stéphanie; Calzone, Laurence; Brabetz, Sebastian; Picard, Daniel; Montagud, Arnau; Liva, Stéphane; Sta, Alexandre; Dingli, Florent; Arras, Guillaume; Rivera, Jaime; Loew, Damarys; Besnard, Aurore; Lacombe, Joëlle; Pagès, Mélanie; Varlet, Pascale; Dufour, Christelle; Yu, Hua; Mercier, Audrey L; Indersie, Emilie; Chivet, Anaïs; Leboucher, Sophie; Sieber, Laura; Beccaria, Kevin; Gombert, Michael; Meyer, Frauke D; Qin, Nan; Bartl, Jasmin; Chavez, Lukas; Okonechnikov, Konstantin; Sharma, Tanvi; Thatikonda, Venu; Bourdeaut, Franck; Pouponnot, Celio; Ramaswamy, Vijay; Korshunov, Andrey; Borkhardt, Arndt; Reifenberger, Guido; Poullet, Patrick; Taylor, Michael D; Kool, Marcel; Pfister, Stefan M; Kawauchi, Daisuke; Barillot, Emmanuel; Remke, Marc; Ayrault, Olivier.
Afiliação
  • Forget A; Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France. Electronic address: antoine.forget@curie.fr.
  • Martignetti L; Institut Curie, 26 rue d'Ulm, 75005 Paris, France; PSL Research University, 75005 Paris, France; Inserm, U900, 75005 Paris, France; Mines Paris Tech, 77305 cedex Fontainebleau, France.
  • Puget S; Department of Pediatric Neurosurgery, Necker University Hospital, University Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.
  • Calzone L; Institut Curie, 26 rue d'Ulm, 75005 Paris, France; PSL Research University, 75005 Paris, France; Inserm, U900, 75005 Paris, France; Mines Paris Tech, 77305 cedex Fontainebleau, France.
  • Brabetz S; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Picard D; Department of Pediatric Neuro-Oncogenomics, DKFZ, Heidelberg, Germany; Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany; Institute of Neuropathology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düss
  • Montagud A; Institut Curie, 26 rue d'Ulm, 75005 Paris, France; PSL Research University, 75005 Paris, France; Inserm, U900, 75005 Paris, France; Mines Paris Tech, 77305 cedex Fontainebleau, France.
  • Liva S; Institut Curie, 26 rue d'Ulm, 75005 Paris, France; PSL Research University, 75005 Paris, France; Inserm, U900, 75005 Paris, France; Mines Paris Tech, 77305 cedex Fontainebleau, France.
  • Sta A; Institut Curie, 26 rue d'Ulm, 75005 Paris, France; PSL Research University, 75005 Paris, France; Inserm, U900, 75005 Paris, France; Mines Paris Tech, 77305 cedex Fontainebleau, France.
  • Dingli F; Proteomics and Mass Spectrometry Laboratory, Institut Curie, PSL Research University, 75005 Paris, France.
  • Arras G; Proteomics and Mass Spectrometry Laboratory, Institut Curie, PSL Research University, 75005 Paris, France.
  • Rivera J; Proteomics and Mass Spectrometry Laboratory, Institut Curie, PSL Research University, 75005 Paris, France.
  • Loew D; Proteomics and Mass Spectrometry Laboratory, Institut Curie, PSL Research University, 75005 Paris, France.
  • Besnard A; Department of Neuropathology, Sainte-Anne Hospital, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.
  • Lacombe J; Department of Neuropathology, Sainte-Anne Hospital, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.
  • Pagès M; Department of Neuropathology, Sainte-Anne Hospital, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.
  • Varlet P; Department of Neuropathology, Sainte-Anne Hospital, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.
  • Dufour C; Department of Pediatric and Adolescent Oncology, Gustave Roussy, Rue Edouard Vaillant, 94805 Villejuif, France.
  • Yu H; Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France.
  • Mercier AL; Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France.
  • Indersie E; Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France.
  • Chivet A; Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France.
  • Leboucher S; Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France; Institut Curie, Centre de Recherche, Plateforme d'Histologie, Orsay 91405, France.
  • Sieber L; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Beccaria K; Department of Pediatric Neurosurgery, Necker University Hospital, University Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.
  • Gombert M; Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
  • Meyer FD; Department of Pediatric Neuro-Oncogenomics, DKFZ, Heidelberg, Germany; Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany; Institute of Neuropathology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düss
  • Qin N; Department of Pediatric Neuro-Oncogenomics, DKFZ, Heidelberg, Germany; Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany; Institute of Neuropathology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düss
  • Bartl J; Department of Pediatric Neuro-Oncogenomics, DKFZ, Heidelberg, Germany; Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany; Institute of Neuropathology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düss
  • Chavez L; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Okonechnikov K; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Sharma T; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Thatikonda V; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Bourdeaut F; Paris-Sciences-Lettres Research University, Institut Curie Research Center, SiRIC, Laboratory of Translational Research in Pediatric Oncology, Paris 75005, France; Paris-Sciences-Lettres Research University, Institut Curie Research Center, INSERM U830, Laboratory of Biology and Genetics of Cancers,
  • Pouponnot C; Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France.
  • Ramaswamy V; Division of Haematology/Oncology, Hospital for Sick Children and Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada.
  • Korshunov A; Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), and Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
  • Borkhardt A; Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
  • Reifenberger G; Institute of Neuropathology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
  • Poullet P; Institut Curie, 26 rue d'Ulm, 75005 Paris, France; PSL Research University, 75005 Paris, France; Inserm, U900, 75005 Paris, France; Mines Paris Tech, 77305 cedex Fontainebleau, France.
  • Taylor MD; Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; Departments
  • Kool M; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Pfister SM; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heide
  • Kawauchi D; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: d.kawauchi@dkfz-heidelberg.de.
  • Barillot E; Institut Curie, 26 rue d'Ulm, 75005 Paris, France; PSL Research University, 75005 Paris, France; Inserm, U900, 75005 Paris, France; Mines Paris Tech, 77305 cedex Fontainebleau, France. Electronic address: emmanuel.barillot@curie.fr.
  • Remke M; Department of Pediatric Neuro-Oncogenomics, DKFZ, Heidelberg, Germany; Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany; Institute of Neuropathology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düss
  • Ayrault O; Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France. Electronic address: olivier.ayrault@curie.fr.
Cancer Cell ; 34(3): 379-395.e7, 2018 09 10.
Article em En | MEDLINE | ID: mdl-30205043
ABSTRACT
The current consensus recognizes four main medulloblastoma subgroups (wingless, Sonic hedgehog, group 3 and group 4). While medulloblastoma subgroups have been characterized extensively at the (epi-)genomic and transcriptomic levels, the proteome and phosphoproteome landscape remain to be comprehensively elucidated. Using quantitative (phospho)-proteomics in primary human medulloblastomas, we unravel distinct posttranscriptional regulation leading to highly divergent oncogenic signaling and kinase activity profiles in groups 3 and 4 medulloblastomas. Specifically, proteomic and phosphoproteomic analyses identify aberrant ERBB4-SRC signaling in group 4. Hence, enforced expression of an activated SRC combined with p53 inactivation induces murine tumors that resemble group 4 medulloblastoma. Therefore, our integrative proteogenomics approach unveils an oncogenic pathway and potential therapeutic vulnerability in the most common medulloblastoma subgroup.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Cerebelares / Quinases da Família src / Receptor ErbB-4 / Meduloblastoma Limite: Adolescent / Animals / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Cerebelares / Quinases da Família src / Receptor ErbB-4 / Meduloblastoma Limite: Adolescent / Animals / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2018 Tipo de documento: Article