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Identification of Candidate Tumour Suppressor Genes Frequently Methylated in Renal Cell Carcinoma

Promoter region hyermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many types of human cancers. Functional epigenetic studies, in which gene expression is induced by treatment with demethylating agents, may identify novel genes with tumo...

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Autores principales: Morris, Mark R., Ricketts, Christopher, Gentle, Dean, Abdulrahman, Mahera, Clarke, Noel, Brown, Michael, Kishida, Takeshi, Yao, Masahiro, Latif, Farida, Maher, Eamonn R
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021900/
https://www.ncbi.nlm.nih.gov/pubmed/20154727
http://dx.doi.org/10.1038/onc.2009.493
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author Morris, Mark R.
Ricketts, Christopher
Gentle, Dean
Abdulrahman, Mahera
Clarke, Noel
Brown, Michael
Kishida, Takeshi
Yao, Masahiro
Latif, Farida
Maher, Eamonn R
author_facet Morris, Mark R.
Ricketts, Christopher
Gentle, Dean
Abdulrahman, Mahera
Clarke, Noel
Brown, Michael
Kishida, Takeshi
Yao, Masahiro
Latif, Farida
Maher, Eamonn R
author_sort Morris, Mark R.
collection PubMed
description Promoter region hyermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many types of human cancers. Functional epigenetic studies, in which gene expression is induced by treatment with demethylating agents, may identify novel genes with tumour-specific methylation. We used high-density gene expression microarrays in a functional epigenetic study of 11 renal cell carcinoma (RCC) cell lines. Twenty eight genes were then selected for analysis of promoter methylation status in cell lines and primary RCC. Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1 and COL15A1) demonstrated frequent (>30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing. Re-expression of BNC1, CST6, RPRM, and SFRP1 suppressed the growth of RCC cell lines and RNAi knock-down of BNC1, SFRP1 and COL14A1 increased the growth of RCC cell lines. Methylation of BNC1 or COL14A1 was associated with a poorer prognosis independent of tumour size, stage or grade. The identification of these epigenetically inactivated candidate RCC tumour suppressor genes can provide insights into renal tumourigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection.
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spelling pubmed-30219002011-01-17 Identification of Candidate Tumour Suppressor Genes Frequently Methylated in Renal Cell Carcinoma Morris, Mark R. Ricketts, Christopher Gentle, Dean Abdulrahman, Mahera Clarke, Noel Brown, Michael Kishida, Takeshi Yao, Masahiro Latif, Farida Maher, Eamonn R Oncogene Article Promoter region hyermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many types of human cancers. Functional epigenetic studies, in which gene expression is induced by treatment with demethylating agents, may identify novel genes with tumour-specific methylation. We used high-density gene expression microarrays in a functional epigenetic study of 11 renal cell carcinoma (RCC) cell lines. Twenty eight genes were then selected for analysis of promoter methylation status in cell lines and primary RCC. Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1 and COL15A1) demonstrated frequent (>30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing. Re-expression of BNC1, CST6, RPRM, and SFRP1 suppressed the growth of RCC cell lines and RNAi knock-down of BNC1, SFRP1 and COL14A1 increased the growth of RCC cell lines. Methylation of BNC1 or COL14A1 was associated with a poorer prognosis independent of tumour size, stage or grade. The identification of these epigenetically inactivated candidate RCC tumour suppressor genes can provide insights into renal tumourigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection. 2010-02-15 2010-04-08 /pmc/articles/PMC3021900/ /pubmed/20154727 http://dx.doi.org/10.1038/onc.2009.493 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Morris, Mark R.
Ricketts, Christopher
Gentle, Dean
Abdulrahman, Mahera
Clarke, Noel
Brown, Michael
Kishida, Takeshi
Yao, Masahiro
Latif, Farida
Maher, Eamonn R
Identification of Candidate Tumour Suppressor Genes Frequently Methylated in Renal Cell Carcinoma
title Identification of Candidate Tumour Suppressor Genes Frequently Methylated in Renal Cell Carcinoma
title_full Identification of Candidate Tumour Suppressor Genes Frequently Methylated in Renal Cell Carcinoma
title_fullStr Identification of Candidate Tumour Suppressor Genes Frequently Methylated in Renal Cell Carcinoma
title_full_unstemmed Identification of Candidate Tumour Suppressor Genes Frequently Methylated in Renal Cell Carcinoma
title_short Identification of Candidate Tumour Suppressor Genes Frequently Methylated in Renal Cell Carcinoma
title_sort identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021900/
https://www.ncbi.nlm.nih.gov/pubmed/20154727
http://dx.doi.org/10.1038/onc.2009.493
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