Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma

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dc.contributor.author Krause, Lutz
dc.contributor.author Nones, Katia
dc.contributor.author Loffler, Kelly A
dc.contributor.author Nancarrow, Derek J
dc.contributor.author Oey, Harald
dc.contributor.author Tang, Yue Hang
dc.contributor.author Wayte, Nicci
dc.contributor.author Patch, Ann-Marie
dc.contributor.author Patel, Kalpana
dc.contributor.author Thomas, Janine
dc.contributor.author Stoye, Jens
dc.contributor.author Hussey, Damian James
dc.contributor.author Watson, David Ian
dc.contributor.author Lord, Reginald V
dc.contributor.author Phillips, Wayne A
dc.contributor.author Gotley, David C
dc.contributor.author Smithers, B Mark
dc.contributor.author Whiteman, David C
dc.contributor.author Hayward, Nicholas K
dc.contributor.author Grimmond, Sean M
dc.contributor.author Waddell, Nicola
dc.contributor.author Barbour, Andrew P
dc.date.accessioned 2016-10-25T23:04:52Z
dc.date.available 2016-10-25T23:04:52Z
dc.date.issued 2016
dc.description This 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.com en
dc.description.abstract The 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.identifier.citation Krause 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.doi https://doi.org/10.1093/carcin/bgw018 en
dc.identifier.issn 0143-3334
dc.identifier.uri http://hdl.handle.net/2328/36470
dc.language.iso en
dc.oaire.license.condition.license CC-BY-NC
dc.publisher Oxford University Press en
dc.relation http://purl.org/au-research/grants/nhmrc/1021403 en
dc.relation.grantnumber NHMRC/1021403 en
dc.rights Copyright © The Author 2016. Published by Oxford University Press. en
dc.rights.holder The Authors en
dc.title Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma en
dc.type Article en
local.contributor.authorOrcidLookup Hussey, Damian James: https://orcid.org/0000-0002-6121-6740 en_US
local.contributor.authorOrcidLookup Loffler, Kelly A: https://orcid.org/0000-0003-3302-5995 en_US
local.contributor.authorOrcidLookup Watson, David Ian: https://orcid.org/0000-0002-7683-2693 en_US
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