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dc.contributor.authorUribe-Lewis, Santiago
dc.contributor.authorStark, Rory
dc.contributor.authorCarroll, Thomas
dc.contributor.authorDunning, Mark J.
dc.contributor.authorBachman, Martin
dc.contributor.authorIto, Yoko
dc.contributor.authorStojic, Lovorka
dc.contributor.authorHalim, Silvia
dc.contributor.authorVowler, Sarah L.
dc.contributor.authorLynch, Andy G.
dc.contributor.authorDelatte, Benjamin
dc.contributor.authorde Bony, Eric J.
dc.contributor.authorColin, Laurence
dc.contributor.authorDefrance, Matthieu
dc.contributor.authorKrueger, Felix
dc.contributor.authorSilva, Ana Luisa
dc.contributor.authorten Hoopen, Rogier
dc.contributor.authorIbrahim, Ashraf E.K.
dc.contributor.authorFuks, François
dc.contributor.authorMurrell, Adele
dc.date.accessioned2017-08-14T12:30:12Z
dc.date.available2017-08-14T12:30:12Z
dc.date.issued2015-04-01
dc.identifier.citationUribe-Lewis , S , Stark , R , Carroll , T , Dunning , M J , Bachman , M , Ito , Y , Stojic , L , Halim , S , Vowler , S L , Lynch , A G , Delatte , B , de Bony , E J , Colin , L , Defrance , M , Krueger , F , Silva , A L , ten Hoopen , R , Ibrahim , A E K , Fuks , F & Murrell , A 2015 , ' 5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer ' , Genome Biology , vol. 16 , 69 . https://doi.org/10.1186/s13059-015-0605-5en
dc.identifier.issn1474-7596
dc.identifier.otherPURE: 250731008
dc.identifier.otherPURE UUID: 082f2f7c-ee28-4ea9-8292-fa3b2c1704af
dc.identifier.otherScopus: 84939211505
dc.identifier.otherORCID: /0000-0002-7876-7338/work/35946877
dc.identifier.urihttp://hdl.handle.net/10023/11446
dc.descriptionThe authors would like to acknowledge the support of The University of Cambridge, Cancer Research UK (CRUK SEB-Institute Group Award A ref10182; CRUK Senior fellowship C10112/A11388 to AEKI) and Hutchison Whampoa Limited. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. FF is a ULB Professor funded by grants from the F.N.R.S. and Télévie, the IUAP P7/03 programme, the ARC (AUWB-2010-2015 ULB-No 7), the WB Health program and the Fonds Gaston Ithier. Data access: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jpwzvsowiyuamzs&acc=GSE47592en
dc.description.abstractBackground : The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced in proliferating cells such as colon tumours and the gut crypt progenitors, from which tumours can arise. Results : Here, we show that colorectal tumours and cancer cells express Ten-Eleven-Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells. Conclusions : Together our results indicate that promoters that acquire 5hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5hmC in tumours. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation.
dc.format.extent15
dc.language.isoeng
dc.relation.ispartofGenome Biologyen
dc.rights© Uribe-Lewis et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectQH301 Biologyen
dc.subjectQH426 Geneticsen
dc.subjectEcology, Evolution, Behavior and Systematicsen
dc.subjectGeneticsen
dc.subjectCell Biologyen
dc.subjectDASen
dc.subject.lccRC0254en
dc.subject.lccQH301en
dc.subject.lccQH426en
dc.title5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in canceren
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Statisticsen
dc.identifier.doihttps://doi.org/10.1186/s13059-015-0605-5
dc.description.statusPeer revieweden


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