Unequivocal delineation of clinicogenetic subgroups and development of a new model for improved outcome prediction in neuroblastoma.
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.
Vandesompele
Jo
J
Center for Medical Genetics Ghent (CMGG), Ghent University Hospital, MRB, De Pintelaan 185, B-9000 Ghent, Belgium. Joke.Vandesompele@UGent.be
Baudis
Michael
M
De Preter
Katleen
K
Van Roy
Nadine
N
Ambros
Peter
P
Bown
Nick
N
Brinkschmidt
Christian
C
Christiansen
Holger
H
Combaret
Valérie
V
Lastowska
Maria
M
Nicholson
James
J
O'Meara
Anne
A
Plantaz
Dominique
D
Stallings
Raymond
R
Brichard
Bénédicte
B
Van den Broecke
Caroline
C
De Bie
Sylvia
S
De Paepe
Anne
A
Laureys
Geneviève
G
Speleman
Frank
F
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