title: Unequivocal delineation of clinicogenetic subgroups and development of a new model for improved outcome prediction in neuroblastoma.
abstract: OBJECTIVE
  Neuroblastoma is a genetically heterogeneous pediatric tumor with a remarkably variable clinical behavior ranging from widely disseminated disease to spontaneous regression. In this study, we aimed for comprehensive genetic subgroup discovery and assessment of independent prognostic markers based on genome-wide aberrations detected by comparative genomic hybridization (CGH).
  
  
  METHODS
  Published CGH data from 231 primary untreated neuroblastomas were converted to a digitized format suitable for global data mining, subgroup discovery, and multivariate survival analyses.
  
  
  RESULTS
  In contrast to previous reports, which included only a few genetic parameters, we present here for the first time a strategy that allows unbiased evaluation of all genetic imbalances detected by CGH. The presented approach firmly established the existence of three different clinicogenetic subgroups and indicated that chromosome 17 status and tumor stage were the only independent significant predictors for patient outcome. Important new findings were: (1) a normal chromosome 17 status as a delineator of a subgroup of presumed favorable-stage tumors with highly increased risk; (2) the recognition of a survivor signature conferring 100% 5-year survival for stage 1, 2, and 4S tumors presenting with whole chromosome 17 gain; and (3) the identification of 3p deletion as a hallmark of older age at diagnosis.
  
  
  CONCLUSIONS
  We propose a new regression model for improved patient outcome prediction, incorporating tumor stage, chromosome 17, and amplification/deletion status. These findings may prove highly valuable with respect to more reliable risk assessment, evaluation of clinical results, and optimization of current treatment protocols.
authors.affiliation: Center for Medical Genetics Ghent (CMGG), Ghent University Hospital, MRB, De Pintelaan 185, B-9000 Ghent, Belgium. Joke.Vandesompele@UGent.be
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.forename: Michael
authors.initials: M
authors.lastname: Baudis
authors.forename: Katleen
authors.initials: K
authors.lastname: De Preter
authors.forename: Nadine
authors.initials: N
authors.lastname: Van Roy
authors.forename: Peter
authors.initials: P
authors.lastname: Ambros
authors.forename: Nick
authors.initials: N
authors.lastname: Bown
authors.forename: Christian
authors.initials: C
authors.lastname: Brinkschmidt
authors.forename: Holger
authors.initials: H
authors.lastname: Christiansen
authors.forename: Valérie
authors.initials: V
authors.lastname: Combaret
authors.forename: Maria
authors.initials: M
authors.lastname: Lastowska
authors.forename: James
authors.initials: J
authors.lastname: Nicholson
authors.forename: Anne
authors.initials: A
authors.lastname: O'Meara
authors.forename: Dominique
authors.initials: D
authors.lastname: Plantaz
authors.forename: Raymond
authors.initials: R
authors.lastname: Stallings
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Brichard
authors.forename: Caroline
authors.initials: C
authors.lastname: Van den Broecke
authors.forename: Sylvia
authors.initials: S
authors.lastname: De Bie
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Geneviève
authors.initials: G
authors.lastname: Laureys
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis