Comment[ArrayExpressAccession]	E-GEOD-32298
MAGE-TAB Version	1.1						
Public Release Date	2012-12-05
Investigation Title	Gene expression changes in 786-O cells in response to 5DC treatment.						
Comment[Submitted Name]	Gene expression changes in 786-O cells in response to 5DC treatment.
Experiment Description	Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway. Gene expression data from 786-O cells after 3-day treatment with 100uM 5’-aza-deoxycytidine (5DC) or vehicle (DMSO).						
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl					
Person Last Name	Vanharanta	Vanharanta	Massagué				
Person First Name	Sakari	Sakari	Joan				
Person Email	vanharas@mskcc.org						
Person Affiliation	Memorial Sloan Kettering Cancer Center						
Person Address	Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, 415 E 68th St., New York, USA						
Person Roles	submitter						
Protocol Name	P-GSE32298-1	P-GSE32298-6	P-GSE32298-5	P-GSE32298-3	P-GSE32298-2	P-GSE32298-4	P-GSE32298-7
Protocol Description	ID_REF =  VALUE = GCRMA signal          GCRMA signal	Standard Affymetrix protocol.	Standard Affymetrix protocol.	PrepEase RNA spin kit (USB)	Standard tissue culture conditions.	Standard Affymetrix protocol.	GCRMA as implemented in the R-package gcrma using the default settings and the custom CDF-file hs133phsentrezgcdf version 10.
Protocol Type	bioassay_data_transformation	image_aquisition	hybridization	nucleic_acid_extraction	grow	labeling	feature_extraction
Experimental Factor Name	COMPOUND						
Experimental Factor Type	compound						
Comment[SecondaryAccession]	GSE32298						
Comment[GEOReleaseDate]	2012-12-05						
Comment[ArrayExpressSubmissionDate]	2011-09-22						
Comment[GEOLastUpdateDate]	2012-12-06						
Comment[AEExperimentType]	transcription profiling by array						
SDRF File	E-GEOD-32298.sdrf.txt