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

M. R. Morris; C. J. Ricketts; D. Gentle; F. McRonald; N. Carli; H. Khalili; M. Brown; T. Kishida; M. Yao; R. E. Banks; N. Clarke; F. Latif; E. R. Maher

doi:10.1038/onc.2010.525

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

M. R. Morris, C. J. Ricketts, D. Gentle, F. McRonald, N. Carli, H. Khalili, M. Brown, T. Kishida, M. Yao, R. E. Banks, N. Clarke, F. Latif, E. R. Maher

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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 (P0.0046). The identification of candidate epigenetically inactivated RCC TSGs provides new insights into renal tumourigenesis. © 2011 Macmillan Publishers Limited All rights reserved.

Original language	English
Pages (from-to)	1390-1401
Number of pages	11
Journal	Oncogene
Volume	30
Issue number	12
DOIs	https://doi.org/10.1038/onc.2010.525
Publication status	Published - 24 Mar 2011

Keywords

epigenetics
methylation
renal cell carcinoma

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/onc.2010.525

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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., & Maher, E. R. (2011). Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. Oncogene, 30(12), 1390-1401. https://doi.org/10.1038/onc.2010.525

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

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 (P0.0046). The identification of candidate epigenetically inactivated RCC TSGs provides new insights into renal tumourigenesis. {\textcopyright} 2011 Macmillan Publishers Limited All rights reserved.",

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AU - Carli, N.

AU - Khalili, H.

AU - Brown, M.

AU - Kishida, T.

AU - Yao, M.

AU - Banks, R. E.

AU - Clarke, N.

AU - Latif, F.

AU - Maher, E. R.

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N2 - 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 (P0.0046). The identification of candidate epigenetically inactivated RCC TSGs provides new insights into renal tumourigenesis. © 2011 Macmillan Publishers Limited All rights reserved.

AB - 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 (P0.0046). The identification of candidate epigenetically inactivated RCC TSGs provides new insights into renal tumourigenesis. © 2011 Macmillan Publishers Limited All rights reserved.

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

Abstract

Keywords

UN SDGs

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