Fibroblasts derived from oesophageal adenocarcinoma differ in DNA methylation profile from normal oesophageal fibroblasts
Fibroblasts derived from oesophageal adenocarcinoma differ in DNA methylation profile from normal oesophageal fibroblasts
Oesophageal adenocarcinoma (OAC) is increasing in incidence and has a poor prognosis. Tumour derived fibroblasts (TDFs) differ functionally from normal fibroblasts (NDFs), and play a pivotal role in cancer. Many of the differences persist through subculture. We measured the DNA methylation profiles of 10 TDFs from OAC with 12 NDF from normal oesophageal mucosa using Infinium HumanMethylation450 Beadchips and found they differed in multidimensional scaling analysis. We identified 4,856 differentially methylated CpGs (DMCs, adjusted p < 0.01 and absolute difference in average β-value > 0.15), of which 3,243 (66.8%) were hypomethylated in TDFs compared to NDFs. Hypermethylated DMCs were enriched at transcription start sites (TSSs) and in CpG islands, and depleted in transcriptional enhancers. Gene ontology analysis of genes with DMCs at TSSs revealed an enrichment of genes involved in development, morphogenesis, migration, adhesion, regulation of processes and response to stimuli. Alpha-smooth muscle actin (α-SMA) is a marker of activated fibroblasts and a poor prognostic indicator in OAC. Hypomethylated DMCs were observed at the TSS of transcript variant 2 of α-SMA, which correlated with an increase in α-SMA protein expression. These data suggest that DNA methylation may contribute to the maintenance of the TDF phenotype.
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Smith, Eric
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Palethorpe, Helen M.
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Hayden, Annette
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Young, Joanne
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Underwood, Timothy
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Drew, Paul
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13 June 2017
Smith, Eric
eea55dbd-46d7-4ab4-83b5-0dab88d2aa1c
Palethorpe, Helen M.
22322e25-f27e-49be-88e2-8b45c02ed050
Hayden, Annette
3a43aee1-3ff0-4182-956d-b6c7b3a7f8be
Young, Joanne
2d8bd442-27f9-44f7-9a6d-0917b4e39f78
Underwood, Timothy
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Drew, Paul
c6122bf4-5d29-4f04-b88a-0ac431de5823
Smith, Eric, Palethorpe, Helen M., Hayden, Annette, Young, Joanne, Underwood, Timothy and Drew, Paul
(2017)
Fibroblasts derived from oesophageal adenocarcinoma differ in DNA methylation profile from normal oesophageal fibroblasts.
Scientific Reports, 7 (1), , [3368].
(doi:10.1038/s41598-017-03501-6).
Abstract
Oesophageal adenocarcinoma (OAC) is increasing in incidence and has a poor prognosis. Tumour derived fibroblasts (TDFs) differ functionally from normal fibroblasts (NDFs), and play a pivotal role in cancer. Many of the differences persist through subculture. We measured the DNA methylation profiles of 10 TDFs from OAC with 12 NDF from normal oesophageal mucosa using Infinium HumanMethylation450 Beadchips and found they differed in multidimensional scaling analysis. We identified 4,856 differentially methylated CpGs (DMCs, adjusted p < 0.01 and absolute difference in average β-value > 0.15), of which 3,243 (66.8%) were hypomethylated in TDFs compared to NDFs. Hypermethylated DMCs were enriched at transcription start sites (TSSs) and in CpG islands, and depleted in transcriptional enhancers. Gene ontology analysis of genes with DMCs at TSSs revealed an enrichment of genes involved in development, morphogenesis, migration, adhesion, regulation of processes and response to stimuli. Alpha-smooth muscle actin (α-SMA) is a marker of activated fibroblasts and a poor prognostic indicator in OAC. Hypomethylated DMCs were observed at the TSS of transcript variant 2 of α-SMA, which correlated with an increase in α-SMA protein expression. These data suggest that DNA methylation may contribute to the maintenance of the TDF phenotype.
Text
127928_2_merged_1493001359
- Accepted Manuscript
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s41598-017-03501-6
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More information
Accepted/In Press date: 2 May 2017
e-pub ahead of print date: 13 June 2017
Published date: 13 June 2017
Identifiers
Local EPrints ID: 412362
URI: http://eprints.soton.ac.uk/id/eprint/412362
ISSN: 2045-2322
PURE UUID: 58375148-eeee-479c-b5e3-f3ea8fcc7870
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Date deposited: 17 Jul 2017 13:32
Last modified: 16 Mar 2024 05:24
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Author:
Eric Smith
Author:
Helen M. Palethorpe
Author:
Annette Hayden
Author:
Joanne Young
Author:
Paul Drew
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