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High Myc pathway activity and low stage of neuronal differentiation associate with poor outcome in neuroblastoma.

Author:
  • Erik Fredlund
  • Markus Ringnér
  • John M Maris
  • Sven Påhlman
Publishing year: 2008
Language: English
Pages: 14094-14099
Publication/Series: Proceedings of the National Academy of Sciences
Volume: 105
Issue: 37
Document type: Journal article
Publisher: National Acad Sciences

Abstract english

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.

Keywords

  • Cancer and Oncology

Other

Published
  • CREATE Health
  • ISSN: 1091-6490
Sven Påhlman
E-mail: sven.pahlman [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

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