Classification of neuroblastoma patients by published gene-expression markers reveals a low sensitivity for unfavorable courses of MYCN non-amplified disease.
Currently, Pubmed lists 385 marker genes for neuroblastoma outcome. Using a customized neuroblastoma-microarray, we evaluated the prognostic impact of the gene-expression pattern of 349 of these candidates (90.6%) in 127 neuroblastoma patients with divergent outcome. By significance analysis of microarrays (SAM) and both uncorrected and Bonferroni-corrected ANOVA, 166/349 (47.5%), 218/349 (62.5%) and 128/349 (36.4%) candidates showed significant differential expression between patients with contrasting outcome. By Prediction Analysis for Microarrays (PAM), a 38-gene-classifier was derived from all markers, which classified patients outcome with an overall accuracy of 78.5%. However, patients with unfavorable outcome of MYCN non-amplified disease were largely misclassified (accuracy: 35%), suggesting that these courses are not identified by current marker genes.
Oberthuer
André
A
Children's Hospital, Department of Pediatric Oncology and Hematology and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Kerpener Strasse 62, D-50924 Cologne, Germany. andre.oberthuer@uk-koeln.de
Warnat
Patrick
P
Kahlert
Yvonne
Y
Westermann
Frank
F
Spitz
Rüdiger
R
Brors
Benedikt
B
Hero
Barbara
B
Eils
Roland
R
Schwab
Manfred
M
Berthold
Frank
F
Fischer
Matthias
M
D000704:Analysis of Variance; D014408:Biomarkers, Tumor; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D009447:Neuroblastoma / Q000145:classification* / Q000235:genetics
D014408:Biomarkers, Tumor