Show simple item record

dc.contributor.authorMorris, M R
dc.contributor.authorRicketts, C J
dc.contributor.authorGentle, D
dc.contributor.authorMcRonald, F
dc.contributor.authorCarli, N
dc.contributor.authorKhalili, H
dc.contributor.authorBrown, Michael D
dc.contributor.authorKishida, T
dc.contributor.authorYao, M
dc.contributor.authorBanks, R E
dc.contributor.authorClarke, Noel W
dc.contributor.authorLatif, F
dc.contributor.authorMaher, E R
dc.date.accessioned2011-07-12T10:38:08Z
dc.date.available2011-07-12T10:38:08Z
dc.date.issued2011-03-24
dc.identifier.citationGenome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. 2011, 30 (12):1390-401 Oncogeneen
dc.identifier.issn1476-5594
dc.identifier.pmid21132003
dc.identifier.doi10.1038/onc.2010.525
dc.identifier.urihttp://hdl.handle.net/10541/135856
dc.description.abstractThe detection of promoter region hypermethylation and transcriptional silencing has facilitated the identification of candidate renal cell carcinoma (RCC) tumour suppressor genes (TSGs). We have used a genome-wide strategy (methylated DNA immunoprecipitation (MeDIP) and whole-genome array analysis in combination with high-density expression array analysis) to identify genes that are frequently methylated and silenced in RCC. MeDIP analysis on 9 RCC tumours and 3 non-malignant normal kidney tissue samples was performed, and an initial shortlist of 56 candidate genes that were methylated by array analysis was further investigated; 9 genes were confirmed to show frequent promoter region methylation in primary RCC tumour samples (KLHL35 (39%), QPCT (19%), SCUBE3 (19%), ZSCAN18 (32%), CCDC8 (35%), FBN2 (34%), ATP5G2 (36%), PCDH8 (58%) and CORO6 (22%)). RNAi knockdown for KLHL35, QPCT, SCUBE3, ZSCAN18, CCDC8 and FBN2 resulted in an anchorage-independent growth advantage. Tumour methylation of SCUBE3 was associated with a significantly increased risk of cancer death or relapse (P=0.0046). The identification of candidate epigenetically inactivated RCC TSGs provides new insights into renal tumourigenesis.
dc.language.isoenen
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshCarcinoma, Renal Cell
dc.subject.meshDNA Methylation
dc.subject.meshFemale
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshGene Silencing
dc.subject.meshGenes, Tumor Suppressor
dc.subject.meshGenome, Human
dc.subject.meshGenome-Wide Association Study
dc.subject.meshHumans
dc.subject.meshImmunoprecipitation
dc.subject.meshKidney Neoplasms
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshPromoter Regions, Genetic
dc.subject.meshYoung Adult
dc.titleGenome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK.en
dc.identifier.journalOncogeneen
html.description.abstractThe detection of promoter region hypermethylation and transcriptional silencing has facilitated the identification of candidate renal cell carcinoma (RCC) tumour suppressor genes (TSGs). We have used a genome-wide strategy (methylated DNA immunoprecipitation (MeDIP) and whole-genome array analysis in combination with high-density expression array analysis) to identify genes that are frequently methylated and silenced in RCC. MeDIP analysis on 9 RCC tumours and 3 non-malignant normal kidney tissue samples was performed, and an initial shortlist of 56 candidate genes that were methylated by array analysis was further investigated; 9 genes were confirmed to show frequent promoter region methylation in primary RCC tumour samples (KLHL35 (39%), QPCT (19%), SCUBE3 (19%), ZSCAN18 (32%), CCDC8 (35%), FBN2 (34%), ATP5G2 (36%), PCDH8 (58%) and CORO6 (22%)). RNAi knockdown for KLHL35, QPCT, SCUBE3, ZSCAN18, CCDC8 and FBN2 resulted in an anchorage-independent growth advantage. Tumour methylation of SCUBE3 was associated with a significantly increased risk of cancer death or relapse (P=0.0046). The identification of candidate epigenetically inactivated RCC TSGs provides new insights into renal tumourigenesis.


This item appears in the following Collection(s)

Show simple item record