title: Emergence of new ALK mutations at relapse of neuroblastoma.
abstract: OBJECTIVE
  In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution.
  
  
  METHODS
  We analyzed ALK mutations in 54 paired diagnosis-relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was observed in one paired sample, a minor mutated component in the other sample was searched for by more than 100,000× deep sequencing of the relevant hotspot, with a sensitivity of 0.17%.
  
  
  RESULTS
  All nine ALK-mutated cases at diagnosis demonstrated the same mutation at relapse, in one case in only one of several relapse nodules. In five additional cases, the mutation seemed to be relapse specific, four of which were investigated by deep sequencing. In two cases, no mutation evidence was observed at diagnosis. In one case, the mutation was present at a subclonal level (0.798%) at diagnosis, whereas in another case, two different mutations resulting in identical amino acid changes were detected, one only at diagnosis and the other only at relapse. Further evidence of clonal evolution of ALK-mutated cells was provided by establishment of a fully ALK-mutated cell line from a primary sample with an ALK-mutated cell population at subclonal level (6.6%).
  
  
  CONCLUSIONS
  In neuroblastoma, subclonal ALK mutations can be present at diagnosis with subsequent clonal expansion at relapse. Given the potential of ALK-targeted therapy, the significant spatiotemporal variation of ALK mutations is of utmost importance, highlighting the potential of deep sequencing for detection of subclonal mutations with a sensitivity 100-fold that of Sanger sequencing and the importance of serial samplings for therapeutic decisions.
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium. gudrun.schleiermacher@curie.net.
authors: Gudrun
authors: G
authors: Schleiermacher
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Niloufar
authors: N
authors: Javanmardi
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Virginie
authors: V
authors: Bernard
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Quentin
authors: Q
authors: Leroy
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Julie
authors: J
authors: Cappo
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Thomas
authors: T
authors: Rio Frio
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Gaelle
authors: G
authors: Pierron
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Eve
authors: E
authors: Lapouble
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Valérie
authors: V
authors: Combaret
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Frank
authors: F
authors: Speleman
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Bram
authors: B
authors: de Wilde
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Anna
authors: A
authors: Djos
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Ingrid
authors: I
authors: Ora
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Fredrik
authors: F
authors: Hedborg
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Catarina
authors: C
authors: Träger
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Britt-Marie
authors: BM
authors: Holmqvist
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Jonas
authors: J
authors: Abrahamsson
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Michel
authors: M
authors: Peuchmaur
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Jean
authors: J
authors: Michon
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Isabelle
authors: I
authors: Janoueix-Lerosey
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Per
authors: P
authors: Kogner
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Olivier
authors: O
authors: Delattre
authors: Gudrun Schleiermacher, Julie Cappo, Isabelle Janoueix-Lerosey, and Olivier Delattre, L'Institut National de la Santé et de la Recherche Médicale U830, Laboratoire de Génétique et Biologie des Cancers; Gudrun Schleiermacher, Virginie Bernard, Quentin Leroy, Thomas Rio Frio, Gaelle Pierron, Eve Lapouble, and Jean Michon, Institut Curie; Michel Peuchmaur, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Service de Pathologie; Michel Peuchmaur, Université Diderot Paris 7, Sorbonne Paris-Cité, Paris; Valérie Combaret, Centre Léon-Bérard, Laboratoire de Recherche Translationnelle, Lyon, France; Niloufar Javanmardi, Anna Djos, Jonas Abrahamsson, and Tommy Martinsson, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg; Ingrid Øra, Lund University, Lund; Fredrik Hedborg, Uppsala University, and Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle; Catarina Träger and Per Kogner, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm; Britt-Marie Holmqvist, Linköping University Hospital, Linköping, Sweden; Frank Speleman and Bram de Wilde, Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Tommy
authors: T
authors: Martinsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002675:Child, Preschool; D004789:Enzyme Activation; D005091:Exons; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics; D009447:Neuroblastoma / Q000201:enzymology* / Q000235:genetics*; D017354:Point Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D055815:Young Adult
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases