title: Clinical characteristics and outcome of patients with neuroblastoma presenting genomic amplification of loci other than MYCN.
abstract: BACKGROUND
  Somatically acquired genomic alterations with MYCN amplification (MNA) are key features of neuroblastoma (NB), the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s) distinct from MYCN.
  
  
  METHODS
  Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected.
  
  
  RESULTS
  In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8) presented regional amplification(s) without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases). This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26) had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22). Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p<0.05).
  
  
  CONCLUSIONS
  NBs harbouring regional amplification(s) without MNA are rare and seem to show atypical features in clinical presentation and genomic profile. Further high resolution genetic explorations are justified in this heterogeneous group, especially when considering these alterations as predictive markers for targeted therapy.
authors.affiliation: Institut Curie, Département de Pédiatrie, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Guimier
authors.affiliation: Institut Curie, Unité de Génétique Somatique, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ferrand
authors.affiliation: Institut Curie, Unité de Génétique Somatique, Paris, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pierron
authors.affiliation: Institut Curie, Unité de Génétique Somatique, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Janoueix-Lerosey
authors.affiliation: Centre Léon Bérard, Laboratoire de recherche translationnelle, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Combaret
authors.affiliation: Institut Curie, Service de biostatistiques, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Mosseri
authors.affiliation: CHU Nantes, Service d'Hémato-Oncologie Pédiatrique, Nantes, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Thebaud
authors.affiliation: CHU Toulouse, Service d'Hémato-Oncologie Pédiatrique, Toulouse, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Gambart
authors.affiliation: CHU Grenoble, Service d'Hémato-Oncologie Pédiatrique, Grenoble, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.affiliation: Institut d'Hématologie et d'Oncologie Pédiatrique, Centre de Lutte contre le Cancer Léon Bérard, Lyon, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
authors.affiliation: Aix-Marseille Univ et APHM, Hôpital d'Enfants de La Timone, Service d'Hématologie-Oncologie Pédiatrique, Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Coze
authors.affiliation: CHU Angers, Service d'Hémato-Oncologie Pédiatrique, Angers, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Rialland
authors.affiliation: Hôpital Trousseau, Service d'Hémato-Oncologie Pédiatrique, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fasola
authors.affiliation: Institut Curie, Unité de Génétique Somatique, Paris, France.
authors.forename: Eve
authors.initials: E
authors.lastname: Lapouble
authors.affiliation: Institut Curie, Laboratoire d'anatomie pathologique, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Fréneaux
authors.affiliation: APHP, hôpital Universitaire Robert Debré, Service de Pathologie, Paris, France, et Université Diderot Paris 7, Sorbonne Paris Cité, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Peuchmaur
authors.affiliation: Institut Curie, Département de Pédiatrie, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Michon
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.affiliation: Institut Curie, Département de Pédiatrie, Paris, France; INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schleiermacher
mesh_terms: D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins