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- aggregation classification "A1".
- aggregation creator B436660.
- aggregation creator B436661.
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- aggregation creator B436664.
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- aggregation creator person.
- aggregation creator person.
- aggregation date "2008".
- aggregation format "application/pdf".
- aggregation hasFormat 518195.bibtex.
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- aggregation hasFormat 518195.dc.
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- aggregation hasFormat 518195.doc.
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- aggregation hasFormat 518195.txt.
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- aggregation hasFormat 518195.yaml.
- aggregation isPartOf urn:issn:1474-760X.
- aggregation language "eng".
- aggregation publisher "BIOMED CENTRAL LTD, CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST,".
- aggregation title "Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas".
- aggregation abstract "Background Amplified MYCN oncogene resulting in deregulated MYCN transcriptional activity is observed in 20% of neuroblastomas and identifies a highly aggressive subtype. In MYCN single-copy neuroblastomas, elevated MYCN mRNA and protein levels are paradoxically associated with a more favorable clinical phenotype, including disseminated tumors that subsequently regress spontaneously (stage 4s-non-amplified). In this study, we asked whether distinct transcriptional MYCN or c-MYC activities are associated with specific neuroblastoma phenotypes. Results We defined a core set of direct MYCN/c-MYC target genes by applying gene expression profiling and Chromatin Immunoprecipitation (ChIP, ChIP-chip) in neuroblastoma cells that allow conditional regulation of MYCN and c-MY C. Their transcript levels were analyzed in 251 primary neuroblastomas. Compared to localized-non-amplified neuroblastomas, MYCN/c-MYC target gene expression gradually increases from stage 4s-non-amplified through stage 4-non-amplified to MYCN amplified tumors. This was associated with MYCN activation in stage 4s-non-amplified and predominantly c-MYC activation in stage 4-nonamplified tumors. A defined set of MYCN/c-MYC target genes was induced in stage 4-nonamplified but not in stage 4s-non-amplified. In line with this, high expression of a subset of MYCN/c-MYC target genes identifies a patient subtype with poor overall survival independent of the established risk markers amplified MYCN, disease stage, and age at diagnosis. Conclusions High MYCN/c-MYC target gene expression is a hallmark of malignant neuroblastoma progression that is predominantly driven by c- MYC in stage 4-non-amplified tumors. In contrast, moderate MYCN function gain in stage 4s-non-amplified tumors induces only a restricted set of target genes that is still compatible with spontaneous regression.".
- aggregation authorList BK761418.
- aggregation issue "10".
- aggregation startPage "R150".
- aggregation volume "9".
- aggregation aggregates 520622.
- aggregation isDescribedBy 518195.
- aggregation similarTo LU-518195.