Transcriptomics

Dataset Information

2

Spinal Ependymoma Gene Expression Data


ABSTRACT: 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. RNA from 35 primary spinal ependymomas (fresh frozen) were isolated by pulverization in liquid nitrogen, and extraction using the Trizol Method (Invitrogen) [PMID:21840481]

ORGANISM(S): Homo sapiens  

SUBMITTER: Stephen C Mack   Michael D Taylor  Stephen Mack Christopher 

PROVIDER: E-GEOD-66787 | ArrayExpress | 2015-09-02

SECONDARY ACCESSION(S): GSE66787PRJNA277960

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications


Myxopapillary ependymoma (MPE) is a distinct histologic 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.Gene e  ...[more]

Similar Datasets

| GSE121476 | GEO
2011-08-14 | E-GEOD-27287 | ArrayExpress
2011-08-14 | E-GEOD-27279 | ArrayExpress
2011-08-15 | GSE27279 | GEO
| GSE27287 | GEO
2016-06-07 | PXD003795 | Pride
2010-11-17 | GSE21507 | GEO
2016-06-06 | PXD003792 | Pride
2011-08-29 | E-GEOD-31715 | ArrayExpress
2010-06-28 | GSE22575 | GEO