期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 37, 页码 14094-14099出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0804455105
关键词
neuroblastoma; pathway analysis; MYCN; Myc; differentiation
资金
- Swedish Knowledge Foundation
- Swedish Cancer Society
- Children's Cancer Foundation of Sweden
- Swedish Research Council
- Swedish Foundation for Strategic Research
- Royal Physiographic Society
- Gunnar Nilssons Cancerstiftelse
- Hans von Kantzow foundation
- Malmo University Hospital
- National Institutes of Health [R01-CA87847, U10-CA98543]
- Alex's Lemonade Stand Foundation
- Abramson Family Cancer Research Institute
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.
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