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Series GSE66787 Query DataSets for GSE66787
Status Public on Sep 02, 2015
Title Spinal Ependymoma Gene Expression Data
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Purpose: Myxopapillary ependymoma (MPE) is a distinct histological variant of ependymoma arising commonly in the spinal cord. Despite an overall favorable prognosis, distant metastases, subarachnoid dissemination, and late recurrences have been reported. Currently the only effective treatment for MPE is gross-total resection. We characterized the genomic and transcriptional landscape of spinal ependymomas in an effort to delineate the genetic basis of this disease and identify new leads for therapy.

Experimental Design: Gene expression profiling was performed on 35 spinal ependymomas. Functional validation experiments were performed on tumour lysates consisting of assays measuring Pyruvate Kinase M activity (PKM), Hexokinase activity (HK), and lactate production.

Results: At a gene expression level, we demonstrate that spinal Grade II and MPE are molecularly and biologically distinct. These findings are supported by specific copy number alterations occurring in each histological variant. Pathway analysis revealed that MPE are characterized by increased cellular metabolism, associated with up-regulation of HIF-1α. These findings were validated by western blot analysis demonstrating increased protein expression of HIF-1α, HK2, PDK1, and phosphorylation of PDHE1A. Functional assays were performed on MPE lysates, which demonstrated decreased PKM activity, increased HK activity, and elevated lactate production.

Conclusions: Our findings suggest that MPE may be driven by a Warburg metabolic phenotype. The key enzymes promoting the Warburg phenotype: HK2, PKM2, and PDK are targetable by small molecule inhibitors/activators, and should be considered for evaluation in future clinical trials for MPE.
Overall design RNA from 35 primary spinal ependymomas (fresh frozen) were isolated by pulverization in liquid nitrogen, and extraction using the Trizol Method (Invitrogen) [PMID:21840481]
Contributor(s) Mack SC, Taylor MD
Citation(s) 25957288
Submission date Mar 11, 2015
Last update date Nov 08, 2016
Contact name Stephen Mack Christopher
Phone 2163182292
Organization name Baylor College of Medicine
Department Pediatrics
Lab Stephen Mack Lab
Street address 1102 Bates Avenue C1030.02
City Houston
State/province TX
ZIP/Postal code 770030
Country USA
Platforms (1)
GPL11532 [HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version]
Samples (35)
GSM1632150 CVTB2384.Primary-Spinal
GSM1632151 CVTB2549.Primary-Spinal
GSM1632152 CVTB2369.Primary-Spinal
BioProject PRJNA277960

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
GSE66787_RAW.tar 154.3 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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