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Series GSE21166 Query DataSets for GSE21166
Status Public on Apr 02, 2010
Title The miR-17/92 Polycistron Is Up-regulated in Sonic Hedgehog-Driven Medulloblastomas and Induced by N-myc in Sonic Hedgehog–Treated Cerebellar Neural Precursors
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Medulloblastoma is the most common malignant pediatric brain tumor, and mechanisms underlying its development are poorly understood. We identified recurrent amplification of the miR-17/92 polycistron proto-oncogene in 6% of pediatric medulloblastomas by high-resolution single-nucleotide polymorphism genotyping arrays and subsequent interphase fluorescence in situ hybridization on a human medulloblastoma tissue microarray. Profiling the expression of 427 mature microRNAs (miRNA) in a series of 90 primary human medulloblastomas revealed that components of the miR-17/92 polycistron are the most highly up-regulated miRNAs in medulloblastoma. Expression of miR-17/92 was highest in the subgroup of medulloblastomas associated with activation of the sonic hedgehog (Shh) signaling pathway compared with other subgroups of medulloblastoma. Medulloblastomas in which miR-17/92 was up-regulated also had elevated levels of MYC/MYCN expression. Consistent with its regulation by Shh, we observed that Shh treatment of primary cerebellar granule neuron precursors (CGNP), proposed cells of origin for the Shh-associated medulloblastomas, resulted in increased miR-17/92 expression. In CGNPs, the Shh effector N-myc, but not Gli1, induced miR-17/92 expression. Ectopic miR-17/92 expression in CGNPs synergized with exogenous Shh to increase proliferation and also enabled them to proliferate in the absence of Shh. We conclude that miR-17/92 is a positive effector of Shh-mediated proliferation and that aberrant expression/amplification of this miR confers a growth advantage to medulloblastomas.
 
Overall design A total of 90 primary medulloblastoma specimens were profiled by Affymetrix exon array and gene-level analysis was performed.
 
Contributor(s) Northcott PA, Fernandez-L A, Hagan JP, Ellison DW, Grajkowska W, Gillespie Y, Grundy R, Van Meter T, Rutka JT, Croce CM, Kenney AM, Taylor MD
Citation(s) 19351822
Submission date Apr 01, 2010
Last update date Feb 18, 2019
Contact name Paul A. Northcott
E-mail(s) panorthcott@gmail.com
Organization name German Cancer Research Center (DKFZ)
Street address Im Neuenheimer Feld 280
City HEIDELBERG
ZIP/Postal code 69120
Country Germany
 
Platforms (1)
GPL5175 [HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]
Samples (90)
GSM529785 Primary medulloblastoma MDT-MB-1 MB90
GSM529786 Primary medulloblastoma MDT-MB-101 MB90
GSM529787 Primary medulloblastoma MDT-MB-103 MB90
Relations
BioProject PRJNA126623

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE21166_RAW.tar 2.0 Gb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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