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E-GEOD-19397 - Expression data identifying hypermethylated genes associated with acquired cisplatin resistance

Status
Submitted on 9 December 2009, released on 12 April 2010, last updated on 1 May 2014
Organism
Homo sapiens
Samples (12)
Array (1)
Protocols (8)
Description
Treatment-related DNA hypermethylation may play a role in creating drug resistant phenotypes by inactivating genes that are required for cytotoxicity, but there have been no genome-wide studies to systematically investigate methylation of individual genes following exposure to chemotherapy. We used microarrays and a pharmacologic unmasking protocol in isogenic cisplatin-sensitive and -resistant cell lines to identify genes that were down-regulated in cisplatin-resistant cells and could be re-activated by the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza-dC). We identified several hundred genes that were down-regulated in each resistant cell line. Of these, 30 genes were common to > 2 cell lines, and/or reported to be down-regulated in previous studies. siRNA knockdown of two candidate genes increased cell viability with cisplatin treatment in sensitive parental cell lines Cisplatin-sensitive and -resistant SCC cells and KB and KB cisplatin-resistant clones (n=2) were split to low density and treated with freshly prepared 5 microM 5-Aza-dC dissolved in 50% acetic acid/50% PBS or were mock treated with the same volume of vehicle in the media for 5 days. Subsequently, RNA was extracted and hybridized on Affymetrix U133A microarrays. Signal intensity and statistical significance was established for each transcript, and a 2-fold decrease in signal in each paired sensitive/resistant cell line in combination with 1.5-fold increase after 5Aza-dC treatment was used to identify candidate genes.
Experiment type
transcription profiling by array 
Contacts
Xiaofei Chang, Constance L Monitto, David Sidransky, Joseph A Califano, Semra Demokan
Citation
Identification of hypermethylated genes associated with cisplatin resistance in human cancers. Chang X, Monitto CL, Demokan S, Kim MS, Chang SS, Zhong X, Califano JA, Sidransky D.
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-19397.idf.txt
Sample and data relationshipE-GEOD-19397.sdrf.txt
Raw data (1)E-GEOD-19397.raw.1.zip
Processed data (1)E-GEOD-19397.processed.1.zip
Array designA-AFFY-33.adf.txt
R ExpressionSetE-GEOD-19397.eSet.r
Links