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Series GSE49162 Query DataSets for GSE49162
Status Public on Aug 15, 2013
Title A Proneural to Mesenchymal Transition Mediated by NFkB Promotes Radiation Resistance in Glioblastoma (part 2)
Organism Homo sapiens
Experiment type Expression profiling by array
Summary SUMMARY Despite numerous genome-wide association studies involving glioblastoma (GBM), few therapeutic targets have been identified for this disease. Using patient derived glioma sphere cultures (GSCs), we have found that a subset of the proneural (PN) GSCs undergo transition to a mesenchymal (MES) state in a TNFa/NFkB dependent manner with an associated enrichment of CD44 sub-populations and radio-resistant phenotypes. To the contrary, MES GSCs exhibit constitutive NFkB activation, CD44 enrichment and radio-resistance. Patients whose tumors exhibit a higher MES metagene, increased expression of CD44, or activated NFkB were associated with poor radiation response and shorter survival. Our results indicate that NFkB activation mediated MES differentiation and radiation resistance presents an attractive therapeutic target for GBM.
SIGNIFICANCE In this study, we show plasticity between the proneural (PN) and mesenchymal (MES) transcriptome signatures observed in glioblastoma (GBM). Specifically, we show that PN glioma sphere cultures (GSCs) can be induced to a MES state with an associated enrichment of CD44 expressing cells and a gain of radio-resistance, which we implicate as NFkB- dependent. Newly diagnosed GBM samples show a direct correlation between radiation response, higher MES metagene, CD44 expression, and NFkB activation. This correlation is also observed in the subset of GBM samples that do not exhibit IDH1 mutation, a favorable prognostic marker. Our results uncover a previously unknown link between subtype plasticity that is regulated by NFkB. Inhibition of NFkB activation can directly impact radio-resistance and presents an attractive therapeutic target for GBM.
 
Overall design 4 treatments
 
Contributor(s) Bhat KL, Balasubramaniyan V, Vaillant B, Ezhilarasan R, Hummelink K, Hollingsworth F, Wani K, Heathcock L, James JD, Goodman LD, Conroy S, Long L, Lelic N, Wang S, Gumin J, Raj D, Kodama Y, Raghunathan A, Olar A, Joshi K, Pelloski CE, Heimberger A, Kim SH, Cahill DP, Rao G, denDunnen WA, Boddeke HM, Phillips HS, Nakano I, Lang FF, Colman H, Sulman EP, Aldape K
Citation(s) 23993863
Submission date Jul 24, 2013
Last update date Jun 26, 2014
Contact name Brian D Vaillant
Organization name Seton Brain and Spine Institute
Department Neurology
Street address 1400 IH 35 Ste300
City Austin
State/province TX
ZIP/Postal code 78701
Country USA
 
Platforms (1)
GPL17486 Affymetrix GeneChip Human Genome U133A 2.0 Array [CDF: HGU133A2_Hs_ENSG_16.0.0]
Samples (4)
GSM1194868 vector control 11GFP
GSM1194869 TNFalpha challenged 11GFP+TNF
GSM1194870 IkappaB repressor 11IKB
This SubSeries is part of SuperSeries:
GSE49009 A Proneural to Mesenchymal Transition Mediated by NFkB Promotes Radiation Resistance in Glioblastoma
Relations
BioProject PRJNA213185

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
GSE49162_RAW.tar 16.9 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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