Methylome profiling reveals functions and genes which are differentially methylated in serrated compared to conventional colorectal carcinoma

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dc.contributor.author Conesa-Zamora, Pablo
dc.contributor.author García-Solano, José es_ES
dc.contributor.author Turpin, María del Carmen es_ES
dc.contributor.author Sebastián-León, Patricia es_ES
dc.contributor.author Torres-Moreno, Daniel es_ES
dc.contributor.author Estrada, Eduardo es_ES
dc.contributor.author Tuomisto, Anne
dc.contributor.author Wilce, Jamie
dc.contributor.author Mäkinen, Markus J.
dc.contributor.author Pérez-Guillermo, Miguel
dc.contributor.author Conesa, Ana es_ES
dc.contributor.other UAM. Departamento de Psicología Social y Metodología es_ES
dc.date.accessioned 2017-03-02T15:06:37Z
dc.date.available 2017-03-02T15:06:37Z
dc.date.issued 2015-09-17
dc.identifier.citation Clinical Epigenetics 7.1 (2015): 101 en_US
dc.identifier.issn 1868-7075 (print) en_US
dc.identifier.issn 1868-7083 (online) en_US
dc.identifier.uri http://hdl.handle.net/10486/677350
dc.description.abstract Background: Serrated adenocarcinoma (SAC) is a recently recognized colorectal cancer (CRC) subtype accounting for 7.5–8.7 % of CRCs. It has been shown that SAC has a worse prognosis and different histological and molecular features compared to conventional carcinoma (CC) but, to date, there is no study analysing its methylome profile. Results: The methylation status of 450,000 CpG sites using the Infinium Human Methylation 450 BeadChip array was investigated in 103 colorectal specimens, including 39 SACs and 34 matched CCs, from Spanish and Finnish patients. Microarray data showed a higher representation of morphogenesis-, neurogenesis-, cytoskeleton- and vesicle transport-related functions and also significant differential methylation of 15 genes, including the iodothyronine deiodinase DIO3 and the forkhead family transcription factor FOXD2 genes which were validated at the CpG, mRNA and protein level using pyrosequencing, methylation-specific PCR, quantitative polymerase chain reaction (qPCR) and immunohistochemistry. A quantification study of the methylation status of CpG sequences in FOXD2 demonstrated a novel region controlling gene expression. Moreover, differences in these markers were also evident when comparing SAC with CRC showing molecular and histological features of high-level microsatellite instability. Conclusions: This methylome study demonstrates distinct epigenetic regulation patterns in SAC which are consistent to previous expression profile studies and that DIO3 and FOXD2 might be molecular targets for a specific histology-oriented treatment of CRC en_US
dc.description.sponsorship This work was supported by a grant from Instituto de Salud Carlos III, Ministerio de Sanidad, Spain (ref: PI12-1232) en_US
dc.format.extent 14 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher BioMed Central en_US
dc.relation.ispartof Clinical Epigenetics en_US
dc.rights This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated en_US
dc.rights © 2015 Conesa-Zamora et al. es_ES
dc.subject.other Colorectal cancer en_US
dc.subject.other CpG island en_US
dc.subject.other DIO3 en_US
dc.subject.other FOXD2 en_US
dc.subject.other Methylome en_US
dc.subject.other Microarray analysis en_US
dc.subject.other Pyrosequencing en_US
dc.subject.other Serrated carcinoma en_US
dc.title Methylome profiling reveals functions and genes which are differentially methylated in serrated compared to conventional colorectal carcinoma en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion https://doi.org/10.1186/s13148-015-0128-7 es_ES
dc.identifier.doi 10.1186/s13148-015-0128-7 es_ES
dc.identifier.publicationfirstpage 101-1 es_ES
dc.identifier.publicationissue 1 es_ES
dc.identifier.publicationlastpage 101-14 es_ES
dc.identifier.publicationvolume 7 es_ES
dc.relation.projectID Gobierno de España. PI12-1232 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en


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