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dc.contributor.authorMorris, MR
dc.contributor.authorGentle, D
dc.contributor.authorAbdulrahman, M
dc.contributor.authorClarke, N
dc.contributor.authorBrown, M
dc.contributor.authorKishida, T
dc.contributor.authorYao, M
dc.contributor.authorTeh, BT
dc.contributor.authorLatif, F
dc.contributor.authorMaher, ER
dc.date.accessioned2019-07-11T13:46:59Z
dc.date.available2019-07-11T13:46:59Z
dc.date.issued2008-01-15
dc.identifier.citationMorris, M. R., Gentle, D., Abdulrahman, M., Clarke, N., Brown, M., Kishida, T., Yao, M., Teh, B. T., Latif, F. and Maher, E. R. (2008) Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma, British Journal of Cancer, 98, pp. 496–501.en
dc.identifier.pmid18195710
dc.identifier.doi10.1038/sj.bjc.6604180en
dc.identifier.urihttp://hdl.handle.net/2436/622540
dc.description.abstractPromoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four RCC cell lines after treatment with the demethylating agent 5-azacytidine. This enabled us to identify HAI-2/SPINT2 as a novel epigenetically inactivated candidate RCC TSG. To identify further candidate TSGs, we undertook bioinformatic and molecular genetic evaluation of a further 60 genes differentially expressed after demethylation. In addition to HAI-2/SPINT2, four genes (PLAU, CDH1, IGFB3 and MT1G) had previously been shown to undergo promoter methylation in RCC. After bioinformatic prioritisation, expression and/or methylation analysis of RCC cell lines ± primary tumours was performed for 34 genes. KRT19 and CXCL16 were methylated in RCC cell lines and primary RCC; however, 22 genes were differentially expressed after demethylation but did not show primary tumour-specific methylation (methylated in normal tissue (n=1); methylated only in RCC cell lines (n=9) and not methylated in RCC cell lines (n=12)). Re-expression of CXCL16 reduced growth of an RCC cell line in vitro. In a summary, a functional epigenomic analysis of four RCC cell lines using microarrays representing 11 000 human genes yielded both known and novel candidate TSGs epigenetically inactivated in RCC, suggesting that this is valid strategy for the identification of novel TSGs and biomarkers. © 2008 Cancer Research UK.en
dc.description.sponsorshipCancer Research UKen
dc.formatapplication/PDFen
dc.languageeng
dc.language.isoenen
dc.publisherSpringer Natureen
dc.relation.urlhttps://www.nature.com/articles/6604180en
dc.subjectCell Line, Tumoren
dc.subjectHumansen
dc.subjectCarcinoma, Renal Cellen
dc.subjectKidney Neoplasmsen
dc.subjectChemokines, CXCen
dc.subjectTransfectionen
dc.subjectGenomicsen
dc.subjectDNA Methylationen
dc.subjectEpigenesis, Geneticen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectGenes, Tumor Suppressoren
dc.subjectReceptors, Scavengeren
dc.subjectGenes, Neoplasmen
dc.subjectNeoplastic Stem Cellsen
dc.subjectPromoter Regions, Geneticen
dc.titleFunctional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinomaen
dc.typeJournal articleen
dc.identifier.eissn1532-1827
dc.identifier.journalBritish Journal of Canceren
dc.date.updated2019-06-24T15:34:18Z
dc.contributor.institutionCancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham B15 2TT, UK.
pubs.place-of-publicationEngland
dc.date.accepted2007-12-05
rioxxterms.funderMedical Research Councilen
rioxxterms.identifier.projectG0500966en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2019-07-11en
dc.source.volume98
dc.source.issue2
dc.source.beginpage496
dc.source.endpage501
dc.description.versionPublished version
refterms.dateFCD2019-07-11T13:46:50Z
refterms.versionFCDVoR
refterms.dateFOA2019-07-11T13:47:00Z


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