title: Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification.
abstract: BACKGROUND
  The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis.
  
  
  METHODS
  To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol.
  
  
  RESULTS
  Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P=0.04). A significant correlation (P=0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) and overall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS=46% vs 75%, P=0.023; OS=66.8% vs 100%, P=0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P=0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P=0.018).
  
  
  CONCLUSIONS
  The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS.
authors.affiliation: Department of Pathology, Istituto Giannina Gaslini, Genova 16148, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Defferrari
authors.affiliation: Department of Pathology, Istituto Giannina Gaslini, Genova 16148, Italy.
authors.forename: K
authors.initials: K
authors.lastname: Mazzocco
authors.affiliation: Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna 1090, Austria.
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authors.initials: IM
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authors.affiliation: Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna 1090, Austria.
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authors.initials: PF
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authors.affiliation: Northern Genetics Service, Newcastle upon Tyne NEI 3 BZ, UK.
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authors.lastname: Bedwell
authors.affiliation: Department of Pathology, Oslo University Hospital Rikshopitalet, Oslo 0424, Norway.
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authors.affiliation: Département de Biologie et de Pathologie Médicales, Gustave Roussy Cancer Campus, Villejuif 94800, France.
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authors.lastname: Bénard
authors.affiliation: Department of Pathology, Medical School of Valencia, University of Valencia, Valencia 46010, Spain.
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authors.affiliation: Northern Genetics Service, Newcastle upon Tyne NEI 3 BZ, UK.
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authors.affiliation: Unité de Génétique Somatique et Cytogénétique, Institut Curie, Paris Cedex 05 75248, France.
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authors.lastname: Couturier
authors.affiliation: Epidemiology, Biostatistics and Committees Unit, Istituto Giannina Gaslini, Genova 16148, Italy.
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authors.affiliation: Department of Pathology, Istituto Giannina Gaslini, Genova 16148, Italy.
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authors.affiliation: Department of Haematology-Oncology, Istituto Giannina Gaslini, Genova 16148, Italy.
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authors.affiliation: Pediatric Oncology Research Unit, Lausanne University Hospital (CHUV), Lausanne 1011, Switzerland.
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authors.affiliation: Epidemiology, Biostatistics and Committees Unit, Istituto Giannina Gaslini, Genova 16148, Italy.
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authors.affiliation: Department of Paediatric Oncology, Southampton General Hospital, Southampton S016 6YD, UK.
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authors.lastname: Lunec
authors.affiliation: Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, Lisbon 1649-016, Portugal.
authors.forename: B
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authors.lastname: Marques
authors.affiliation: Department of Clinical Genetics, Göteborg University, Sahlgrenska University Hospital, Göteborg 413 45, Sweden.
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authors.lastname: Martinsson
authors.affiliation: Department of Pathology, Medical School of Valencia, University of Valencia, Valencia 46010, Spain.
authors.forename: R
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authors.lastname: Noguera
authors.affiliation: Institute of Electronics, Computer and Telecommunication Engineering, National Research Council, Genova 16149, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Parodi
authors.affiliation: 1] INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Paris Cedex 05 75248, France [2] Département d'Oncologie Pédiatrique, Institut Curie, Paris Cedex 05 75248, France.
authors.forename: G
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authors.lastname: Schleiermacher
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle NE2 4HH, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Tweddle
authors.affiliation: Département de Biologie et de Pathologie Médicales, Gustave Roussy Cancer Campus, Villejuif 94800, France.
authors.forename: A
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authors.lastname: Valent
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent 9000, Belgium.
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authors.lastname: Van Roy
authors.affiliation: Department of Paediatric Haematology and Oncology, Charles University and University Hospital Motol, Prague 15008, Czech Republic.
authors.forename: A
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authors.lastname: Vicha
authors.affiliation: Department of Hematology, Hospital Universitari i Politècnic La Fe, Valencia 46009, Spain.
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authors.initials: E
authors.lastname: Villamon
authors.affiliation: Laboratory of Neuroblastoma, Onco/Haematology Laboratory, University of Padua, Pediatric Research Institute (IRP)-Città della Speranza, Corso Stati Uniti 4, Padova 35127, Italy.
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mesh_terms: D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D018572:Disease-Free Survival; D005784:Gene Amplification; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D010524:Peripheral Nervous System Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011379:Prognosis
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins