Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/114713
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Type: Journal article
Title: Fibroblasts derived from oesophageal adenocarcinoma differ in DNA methylation profile from normal oesophageal fibroblasts
Author: Smith, E.
Palethorpe, H.
Hayden, A.
Young, J.
Underwood, T.
Drew, P.
Citation: Scientific Reports, 2017; 7(1):3368-1-3368-9
Publisher: Nature Publishing Group
Issue Date: 2017
ISSN: 2045-2322
2045-2322
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Responsibility: 
Eric Smith, Helen M. Palethorpe, Annette L. Hayden, Joanne P. Young, Timothy J. Underwood and Paul A. Drew
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.
Keywords: Cells, Cultured; Fibroblasts; Humans; Adenocarcinoma; Esophageal Neoplasms; DNA Methylation; Gene Expression Regulation, Neoplastic; CpG Islands; Genome, Human; Transcription Initiation Site; Aged; Aged, 80 and over; Middle Aged; Female; Male; Biomarkers, Tumor
Rights: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 0030071620
DOI: 10.1038/s41598-017-03501-6
Appears in Collections:Medicine publications

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