Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma.
dc.contributor.author | Morris, M R | |
dc.contributor.author | Ricketts, C J | |
dc.contributor.author | Gentle, D | |
dc.contributor.author | McRonald, F | |
dc.contributor.author | Carli, N | |
dc.contributor.author | Khalili, H | |
dc.contributor.author | Brown, Michael D | |
dc.contributor.author | Kishida, T | |
dc.contributor.author | Yao, M | |
dc.contributor.author | Banks, R E | |
dc.contributor.author | Clarke, Noel W | |
dc.contributor.author | Latif, F | |
dc.contributor.author | Maher, E R | |
dc.date.accessioned | 2011-07-12T10:38:08Z | |
dc.date.available | 2011-07-12T10:38:08Z | |
dc.date.issued | 2011-03-24 | |
dc.identifier.citation | Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. 2011, 30 (12):1390-401 Oncogene | en |
dc.identifier.issn | 1476-5594 | |
dc.identifier.pmid | 21132003 | |
dc.identifier.doi | 10.1038/onc.2010.525 | |
dc.identifier.uri | http://hdl.handle.net/10541/135856 | |
dc.description.abstract | The 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.iso | en | en |
dc.subject.mesh | Adult | |
dc.subject.mesh | Aged | |
dc.subject.mesh | Carcinoma, Renal Cell | |
dc.subject.mesh | DNA Methylation | |
dc.subject.mesh | Female | |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | |
dc.subject.mesh | Gene Silencing | |
dc.subject.mesh | Genes, Tumor Suppressor | |
dc.subject.mesh | Genome, Human | |
dc.subject.mesh | Genome-Wide Association Study | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Immunoprecipitation | |
dc.subject.mesh | Kidney Neoplasms | |
dc.subject.mesh | Male | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Promoter Regions, Genetic | |
dc.subject.mesh | Young Adult | |
dc.title | Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. | en |
dc.type | Article | en |
dc.contributor.department | Cancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK. | en |
dc.identifier.journal | Oncogene | en |
html.description.abstract | The 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)
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All Christie Publications
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All Paterson Institute for Cancer Research
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Urological Oncology
Urological Oncology