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

Oncogene volume 30, pages 1390–1401 (2011)Cite this article

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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.

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Acknowledgements

We thank Cancer Research UK for financial support.

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Author notes

  1. M R Morris

    Present address: 8Current address: School of Applied Sciences, University of Wolverhampton, Wolverhampton WV1 1LY, UK.,

Authors and Affiliations

  1. Cancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK

    M R Morris, C J Ricketts, D Gentle, F McRonald, F Latif & E R Maher

  2. Department of Medical and Molecular Genetics, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

    M R Morris, C J Ricketts, D Gentle, F McRonald, N Carli, H Khalili, F Latif & E R Maher

  3. Centre for Rare Diseases and Personalised Medicine. University of Birmingham, Birmingham, UK

    M R Morris, C J Ricketts, D Gentle, F Latif & E R Maher

  4. Paterson Institute for Cancer Research, University of Manchester, Manchester, UK

    M Brown & N Clarke

  5. Department of Urology, Yokohama City University School of Medicine, Yokohama, Japan

    T Kishida & M Yao

  6. Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre, St James's University Hospital, Beckett Street, Leeds, UK,

    R E Banks

  7. West Midlands Region Genetics Service, Birmingham Women's Hospital, Edgbaston, Birmingham, UK

    E R Maher

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Correspondence to E R Maher.

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Morris, M., Ricketts, C., Gentle, D. et al. Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. Oncogene 30, 1390–1401 (2011). https://doi.org/10.1038/onc.2010.525

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