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Scholarly Communication

Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma

Morris, M.R.; Ricketts, C.J.; Gentle, D.; McRonald, F.; Carli, N.; Khalili, H.; Brown, M.; Kishida, T.; Yao, M.; Banks, R.E.; Clarke, N.; Latif, F. and Maher, E.R. (2011) Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. Oncogene, 30 (12). pp. 1390-1401. ISSN 1476-5594 (Online); 0950-9232 (Print)

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The detection of promoter region hyermethylation and transcriptional silencing has facilitated the identification of candidate renal cell carcinoma (RCC) tumour suppressor genes (TSGs). We have utilised 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 were 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 knock-down 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.

Item Type:Article
Additional Information:Advance online publication, 6 December 2010. Issue date : March 2011. Published under auspices of Nature Publishing Group, an imprint of Macmillan Publishers Limited.
Uncontrolled Keywords:Renal cell carcinoma; methylation; epigenetics
Subjects:R Medicine > RK Dentistry
Departments, Research Centres and Related Units:Academic Faculties, Institutes and Research Centres > Faculty of Medicine > School of Dental Sciences
ID Code:1405
Deposited On:15 Mar 2011 14:31
Last Modified:06 Oct 2011 10:09

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