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microRNA Profiling Identifies Cancer-Specific and Prognostic Signatures in Pediatric Malignancies
Purpose: microRNAs have been shown to be involved in different human cancers. We therefore have performed expression profiles on a panel of pediatric tumors to identify cancer-specific microRNAs. We also investigated if microRNAs are coregulated with their host gene. Experimental Design: We performe...
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Published in: | Clinical cancer research 2009-09, Vol.15 (17), p.5560-5568 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Purpose: microRNAs have been shown to be involved in different human cancers. We therefore have performed expression profiles on a
panel of pediatric tumors to identify cancer-specific microRNAs. We also investigated if microRNAs are coregulated with their
host gene.
Experimental Design: We performed parallel microRNAs and mRNA expression profiling on 57 tumor xenografts and cell lines representing 10 different
pediatric solid tumors using microarrays. For those microRNAs that map to their host mRNA, we calculated correlations between
them.
Results: We found that the majority of cancer types clustered together based on their global microRNA expression profiles by unsupervised
hierarchical clustering. Fourteen microRNAs were significantly differentially expressed between rhabdomyosarcoma and neuroblastoma,
and 8 of them were validated in independent patient tumor samples. Exploration of the expression of microRNAs in relationship
with their host genes showed that the expression for 43 of 68 (63%) microRNAs located inside known coding genes was significantly
correlated with that of their host genes. Among these 43 microRNAs, 5 of 7 microRNAs in the OncomiR-1 cluster correlated significantly
with their host gene MIRHG1 ( P < 0.01). In addition, high expression of MIRHG1 was significantly associated with high stage and MYCN amplification in neuroblastoma tumors, and the expression level of MIRHG1 could predict the outcome of neuroblastoma patients independently from the current neuroblastoma risk-stratification in two
independent patient cohorts.
Conclusion: Pediatric cancers express cancer-specific microRNAs. The high expression of the OncomiR-1 host gene MIRHG1 correlates with poor outcome for patients with neuroblastoma, indicating important oncogenic functions of this microRNA cluster
in neuroblastoma biology. (Clin Cancer Res 2009;15(17):5560â8) |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-08-3287 |