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

Mark R. Morris | Zendy; Christopher J. Ricketts | Zendy; Dean Gentle | Zendy; Fiona E. McRonald | Zendy; Natasha Carli | Zendy; Hafez S. Khalili | Zendy; M.D. Brown | Zendy; Takeshi Kishida | Zendy; Masahiro Yao | Zendy; Rosamonde E. Banks | Zendy; Noel W. Clarke | Zendy; Farida Latif | Zendy; Eamonn R. Maher | Zendy

Open Access

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

Author(s) -

Mark R. Morris,

Christopher J. Ricketts,

Dean Gentle,

Fiona E. McRonald,

Natasha Carli,

Hafez S. Khalili,

M.D. Brown,

Takeshi Kishida,

Masahiro Yao,

Rosamonde E. Banks,

Noel W. Clarke,

Farida Latif,

Eamonn R. Maher

Publication year - 2010

Publication title -

oncogene

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.395

H-Index - 342

eISSN - 1476-5594

pISSN - 0950-9232

DOI - 10.1038/onc.2010.525

Subject(s) - biology , candidate gene , dna methylation , methylated dna immunoprecipitation , gene knockdown , methylation , cancer research , carcinogenesis , gene , gene silencing , suppressor , cancer , genome , genetics , microbiology and biotechnology , gene expression

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.

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