Fibroblasts derived from oesophageal adenocarcinoma differ in DNA methylation profile from normal oesophageal fibroblasts

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dc.contributor.authorSmith, E.
dc.contributor.authorPalethorpe, H.
dc.contributor.authorHayden, A.
dc.contributor.authorYoung, J.
dc.contributor.authorUnderwood, T.
dc.contributor.authorDrew, P.
dc.date.issued2017
dc.description.abstractOesophageal 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.
dc.description.statementofresponsibilityEric Smith, Helen M. Palethorpe, Annette L. Hayden, Joanne P. Young, Timothy J. Underwood and Paul A. Drew
dc.identifier.citationScientific Reports, 2017; 7(1):3368-1-3368-9
dc.identifier.doi10.1038/s41598-017-03501-6
dc.identifier.issn2045-2322
dc.identifier.issn2045-2322
dc.identifier.orcidSmith, E. [0000-0003-2958-3492]
dc.identifier.orcidPalethorpe, H. [0000-0003-3803-5113]
dc.identifier.orcidYoung, J. [0000-0002-1514-1522]
dc.identifier.orcidDrew, P. [0000-0001-5661-4771]
dc.identifier.urihttp://hdl.handle.net/2440/114713
dc.language.isoen
dc.publisherNature Publishing Group
dc.rightsOpen 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/.
dc.source.urihttps://doi.org/10.1038/s41598-017-03501-6
dc.subjectCells, Cultured
dc.subjectFibroblasts
dc.subjectHumans
dc.subjectAdenocarcinoma
dc.subjectEsophageal Neoplasms
dc.subjectDNA Methylation
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectCpG Islands
dc.subjectGenome, Human
dc.subjectTranscription Initiation Site
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectBiomarkers, Tumor
dc.titleFibroblasts derived from oesophageal adenocarcinoma differ in DNA methylation profile from normal oesophageal fibroblasts
dc.typeJournal article
pubs.publication-statusPublished

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