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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
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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.
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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.
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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
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Organization name |
Imperial College London
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Department |
Sugery and Cancer
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Lab |
Epigenetics
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Street address |
Du Cane Road
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City |
London |
ZIP/Postal code |
W12 0NN |
Country |
United Kingdom |
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Platforms (1) |
GPL8490 |
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2) |
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Samples (39)
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Relations |
BioProject |
PRJNA169077 |