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dc.contributor.authorMassie, Charles E.
dc.contributor.authorSpiteri, Inmaculada
dc.contributor.authorRoss-Adams, Helen
dc.contributor.authorLuxton, Hayley
dc.contributor.authorKay, Jonathan
dc.contributor.authorWhitaker, Hayley C.
dc.contributor.authorDunning, Mark J.
dc.contributor.authorLamb, Alastair D.
dc.contributor.authorRamos-Montoya, Antonio
dc.contributor.authorBrewer, Daniel S.
dc.contributor.authorCooper, Colin S.
dc.contributor.authorEeles, Rosalind
dc.contributor.authorWarren, Anne Y.
dc.contributor.authorTavaré, Simon
dc.contributor.authorNeal, David E.
dc.contributor.authorLynch, Andy G.
dc.contributor.authorUK Prostate ICGC Group
dc.date.accessioned2017-08-15T11:30:45Z
dc.date.available2017-08-15T11:30:45Z
dc.date.issued2015-04-01
dc.identifier.citationMassie , C E , Spiteri , I , Ross-Adams , H , Luxton , H , Kay , J , Whitaker , H C , Dunning , M J , Lamb , A D , Ramos-Montoya , A , Brewer , D S , Cooper , C S , Eeles , R , Warren , A Y , Tavaré , S , Neal , D E , Lynch , A G & UK Prostate ICGC Group 2015 , ' HES5 silencing is an early and recurrent change in prostate tumourigenesis ' , Endocrine-Related Cancer , vol. 22 , no. 2 , pp. 131-144 . https://doi.org/10.1530/ERC-14-0454en
dc.identifier.issn1351-0088
dc.identifier.otherPURE: 250731582
dc.identifier.otherPURE UUID: ce635149-77f1-4767-b304-ae9da0579842
dc.identifier.otherScopus: 84929310043
dc.identifier.otherORCID: /0000-0002-7876-7338/work/35946876
dc.identifier.urihttp://hdl.handle.net/10023/11471
dc.descriptionThe ICGC Prostate UK Group is funded by Cancer Research UK Grant C5047/A14835, by the Dallaglio Foundation, and by The Wellcome Trust. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre.en
dc.description.abstractProstate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation profiling in a series of multifocal prostate tumours, we identify promoter methylation of the transcription factor HES5 as an early event in prostate tumourigenesis. We confirm that this epigenetic alteration occurs in 86-97% of cases in two independent prostate cancer cohorts (n=49 and n=39 tumour-normal pairs). Treatment of prostate cancer cells with the demethylating agent 5-aza-2′-deoxycytidine increased HES5 expression and downregulated its transcriptional target HES6, consistent with functional silencing of the HES5 gene in prostate cancer. Finally, we identify and test a transcriptional module involving the AR, ERG, HES1 and HES6 and propose a model for the impact of HES5 silencing on tumourigenesis as a starting point for future functional studies.
dc.format.extent14
dc.language.isoeng
dc.relation.ispartofEndocrine-Related Canceren
dc.rights© 2015 The authors. Published by Bioscientifica Ltd. This work is licensed under a Creative Commons Attribution 3.0 Unported License.en
dc.subjectARen
dc.subjectEpigeneticsen
dc.subjectERGen
dc.subjectHES5en
dc.subjectHES6en
dc.subjectMethylationen
dc.subjectNOTCHen
dc.subjectProstate canceren
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectEndocrinology, Diabetes and Metabolismen
dc.subjectOncologyen
dc.subjectEndocrinologyen
dc.subjectCancer Researchen
dc.subjectNDASen
dc.subject.lccRC0254en
dc.titleHES5 silencing is an early and recurrent change in prostate tumourigenesisen
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/10.1530/ERC-14-0454
dc.description.statusPeer revieweden
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=84929310043&partnerID=8YFLogxKen


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