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Series GSE38860 Query DataSets for GSE38860
Status Public on Jan 01, 2013
Title Aberrant DNA methylation at genes associated with a stem cell-like phenotype in cholangiocarcinoma tumors
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Genetic abnormalities of cholangiocarcinoma have been widely studied; however, epigenomic changes related to cholangiocarcinogenesis have been less well characterised. We have profiled the DNA methylomes of 28 primary cholangiocarcinoma and six matched adjacent normal tissues using Infinium’s HumanMethylation27 BeadChips with the aim of identifying gene sets aberrantly epigenetically regulated in this tumour type.
Using a linear model for microarray data we identified 1610 differentially methylated autosomal CpG sites with 809 CpG sites (representing 603 genes) being hypermethylated and 801 CpG sites (representing 712 genes) being hypomethylated in cholangiocarcinoma versus adjacent normal tissues (false discovery rate ≤ 0.05). Gene ontology and gene set enrichment analyses identified gene sets significantly associated with hypermethylation at linked CpG sites in cholangiocarcinoma including homeobox genes and target genes of PRC2, EED, SUZ12 and histone H3 trimethylation at lysine 27. We confirmed frequent hypermethylation at the homeobox genes HOXA9 and HOXD9 by bisulfite pyrosequencing in a larger cohort of cholangiocarcinoma (n = 102).
Our findings indicate a key role for hypermethylation of multiple CpG sites at genes associated with a stem cell-like phenotype as a common molecular aberration in cholangiocarcinoma. These data have implications for cholangiocarcinogenesis, as well as possible novel treatment options using histone methyltransferase inhibitors.
 
Overall design Array-based methylation profiling was performed using the Infinium HumanMethylation27 BeadChip in 28 primary cholangiocarcinomas and six matched adjacent normal tissues. The reproducibility of the Infinium HumanMethylation27 BeadChips was evaluated using five technical replicates of the ovarian cancer cell line PEO1. Differential methylation cutoff was estimated from five technical replicates by bootstrap resampling and set at Δβ ≥ 0.15 corresponding to a FDR ≤ 0.05.
 
Contributor(s) Sriraksa R, Zeller C, Dai W, Siddiq A, Walley AJ, Limpaiboon T, Brown R
Citation(s) 24089088
Submission date Jun 21, 2012
Last update date Jan 02, 2015
Contact name Wei Dai
E-mail(s) w.dai@imperial.ac.uk
Organization name Imperial College London
Department Sugery and Cancer
Lab Epigenetics
Street address Du Cane Road
City London
ZIP/Postal code W12 0NN
Country United Kingdom
 
Platforms (1)
GPL8490 Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2)
Samples (39)
GSM950801 PEO1
GSM950802 PEO1, technical rep 1
GSM950803 PEO1, technical rep 2
Relations
BioProject PRJNA169077

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
GSE38860_RAW.tar 5.8 Mb (http)(custom) TAR
GSE38860_methylated_unmethylated_for_tumor_28.txt.gz 261.6 Kb (ftp)(http) TXT
GSE38860_methylated_unmethylated_signals.txt.gz 6.3 Mb (ftp)(http) TXT
Processed data included within Sample table

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