title: High Myc pathway activity and low stage of neuronal differentiation associate with poor outcome in neuroblastoma.
abstract: The childhood cancer neuroblastoma arises in the developing sympathetic nervous system and is a genotypically and phenotypically heterogeneous disease. Prognostic markers of poor survival probability include amplification of the MYCN oncogene and an undifferentiated morphology. Whereas these features discriminate high- from low-risk patients with precision, identification of poor outcome low- and intermediate-risk patients is more challenging. In this study, we analyze two large neuroblastoma microarray datasets using a priori-defined gene expression signatures. We show that differential overexpression of Myc transcriptional targets and low expression of genes involved in sympathetic neuronal differentiation predicts relapse and death from disease. This was evident not only for high-risk patients but was also robust in identifying groups of poor prognosis patients who were otherwise judged to be at low- or intermediate-risk for adverse outcome. These data suggest that pathway-specific gene expression profiling might be useful in the clinic to adjust treatment strategies for children with neuroblastoma.
authors.affiliation: Center for Molecular Pathology, Department of Laboratory Medicine, CREATE Health, University Hospital MAS, Lund University, SE-205 02 Malmö, Sweden. erik.fredlund@med.lu.se
authors.forename: Erik
authors.initials: E
authors.lastname: Fredlund
authors.forename: Markus
authors.initials: M
authors.lastname: Ringnér
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Sven
authors.initials: S
authors.lastname: Påhlman
mesh_terms: D002454:Cell Differentiation; D005500:Follow-Up Studies; D005784:Gene Amplification; D020869:Gene Expression Profiling; D006801:Humans; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D015398:Signal Transduction; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D016271:Proto-Oncogene Proteins c-myc
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