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dc.contributor.authorKrause, Lutz
dc.contributor.authorNones, Katia
dc.contributor.authorLoffler, Kelly A
dc.contributor.authorNancarrow, Derek J
dc.contributor.authorOey, Harald
dc.contributor.authorTang, Yue Hang
dc.contributor.authorWayte, Nicci
dc.contributor.authorPatch, Ann-Marie
dc.contributor.authorPatel, Kalpana
dc.contributor.authorThomas, Janine
dc.contributor.authorStoye, Jens
dc.contributor.authorHussey, Damian James
dc.contributor.authorWatson, David Ian
dc.contributor.authorLord, Reginald V
dc.contributor.authorPhillips, Wayne A
dc.contributor.authorGotley, David C
dc.contributor.authorSmithers, B Mark
dc.contributor.authorWhiteman, David C
dc.contributor.authorHayward, Nicholas K
dc.contributor.authorGrimmond, Sean M
dc.contributor.authorWaddell, Nicola
dc.contributor.authorBarbour, Andrew P
dc.date.accessioned2016-10-25T23:04:52Z
dc.date.available2016-10-25T23:04:52Z
dc.date.issued2016
dc.identifier.citationKrause L, Nones K, Loffler KA, et al. Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma. Carcinogenesis. 2016;37(4):356-365. doi:10.1093/carcin/bgw018.en
dc.identifier.issn0143-3334
dc.identifier.urihttp://hdl.handle.net/2328/36470
dc.descriptionThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comen
dc.description.abstractThe incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett’s esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival.en
dc.language.isoen
dc.publisherOxford University Pressen
dc.relationhttp://purl.org/au-research/grants/nhmrc/1021403en
dc.rightsCopyright © The Author 2016. Published by Oxford University Press.en
dc.titleIdentification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinomaen
dc.typeArticleen
dc.relation.grantnumberNHMRC/1021403en
dc.identifier.doihttps://doi.org/10.1093/carcin/bgw018en
dc.rights.holderThe Authorsen
dc.rights.licenseCC-BY-NC
local.contributor.authorOrcidLookupHussey, Damian James: https://orcid.org/0000-0002-6121-6740en_US
local.contributor.authorOrcidLookupLoffler, Kelly A: https://orcid.org/0000-0003-3302-5995en_US
local.contributor.authorOrcidLookupWatson, David Ian: https://orcid.org/0000-0002-7683-2693en_US


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