Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma.
Authors
Morris, M RRicketts, C J
Gentle, D
McRonald, F
Carli, N
Khalili, H
Brown, Michael D
Kishida, T
Yao, M
Banks, R E
Clarke, Noel W
Latif, F
Maher, E R
Affiliation
Cancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK.Issue Date
2011-03-24
Metadata
Show full item recordAbstract
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.Citation
Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. 2011, 30 (12):1390-401 OncogeneJournal
OncogeneDOI
10.1038/onc.2010.525PubMed ID
21132003Type
ArticleLanguage
enISSN
1476-5594ae974a485f413a2113503eed53cd6c53
10.1038/onc.2010.525
Scopus Count
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