ZIABC011001 (ZIA) | |||
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Title | Micro RNA Profiling in Pediatric Cancers | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Khan, Javed | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $95,792 | Project Dates | 10/01/2007 - N/A |
Fiscal Year | 2012 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) Childhood Cancers (100.0%) |
Brain (5.0%) Central Nervous System - Not Including Brain (5.0%) Kidney Cancer (5.0%) Kidney Disease (5.0%) Nervous System (40.0%) Neuroblastoma (30.0%) Sarcoma (55.0%) Urinary System (5.0%) |
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Research Type | |||
Cancer Initiation: Oncogenes and Tumor Suppressor Genes Technology Development and/or Marker Discovery |
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Abstract | |||
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 cancerspecific 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 microRNAcluster in neuroblastoma biology. (Clin Cancer Res 2009;15(17):55608) |