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

Fredlund, Erik LU ; Ringnér, Markus LU ; Maris, John M and Påhlman, Sven LU (2008) In Proceedings of the National Academy of Sciences 105(37). p.14094-14099
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... (More)
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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
105
issue
37
pages
14094 - 14099
publisher
National Acad Sciences
external identifiers
  • wos:000259438500074
  • pmid:18780787
  • scopus:52949154642
ISSN
1091-6490
DOI
10.1073/pnas.0804455105
project
CREATE Health
language
English
LU publication?
yes
id
aae27d0d-f577-4c9d-aa1b-159be1ffabb4 (old id 1243221)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18780787?dopt=Abstract
date added to LUP
2008-10-07 13:33:21
date last changed
2017-09-17 08:08:13
@article{aae27d0d-f577-4c9d-aa1b-159be1ffabb4,
  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.},
  author       = {Fredlund, Erik and Ringnér, Markus and Maris, John M and Påhlman, Sven},
  issn         = {1091-6490},
  language     = {eng},
  number       = {37},
  pages        = {14094--14099},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {High Myc pathway activity and low stage of neuronal differentiation associate with poor outcome in neuroblastoma.},
  url          = {http://dx.doi.org/10.1073/pnas.0804455105},
  volume       = {105},
  year         = {2008},
}