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dc.contributor.authorMcRonald, Fiona E
dc.contributor.authorMorris, Mark R
dc.contributor.authorGentle, Dean
dc.contributor.authorWinchester, Laura
dc.contributor.authorBaban, Dilair
dc.contributor.authorRagoussis, Jiannis
dc.contributor.authorClarke, Noel W
dc.contributor.authorBrown, Michael D
dc.contributor.authorKishida, Takeshi
dc.contributor.authorYao, Masahiro
dc.contributor.authorLatif, Farida
dc.contributor.authorMaher, Eamonn R
dc.date.accessioned2009-11-05T10:16:30Z
dc.date.available2009-11-05T10:16:30Z
dc.date.issued2009
dc.identifier.citationCpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma. 2009, 8:31 Mol. Canceren
dc.identifier.issn1476-4598
dc.identifier.pmid19493342
dc.identifier.doi10.1186/1476-4598-8-31
dc.identifier.urihttp://hdl.handle.net/10541/85374
dc.description.abstractBACKGROUND: Renal cell carcinoma (RCC) is histopathologically heterogeneous with clear cell and papillary the most common subtypes. The most frequent molecular abnormality in clear cell RCC is VHL inactivation but promoter methylation of tumour suppressor genes is common in both subtypes of RCC. To investigate whether RCC CpG methylation status was influenced by histopathology and VHL status we performed high-throughput epigenetic profiling using the Illumina Goldengate Methylation Array in 62 RCC (29 RCC from von Hippel-Lindau (VHL) disease patients, 20 sporadic clear cell RCC with wild type VHL and 13 sporadic papillary RCC). RESULTS: 43 genes were methylated in >20% of primary RCC (range 20-45%) and most (37/43) of these had not been reported previously to be methylated in RCC. The distribution of the number of methylated CpGs in individual tumours differed from the expected Poisson distribution (p < 0.00001; log-likelihood G test) suggesting that a subset of RCC displayed a CpG Island Methylator Phenotype. Comparison of RCC subtypes revealed that, on average, tumour specific CpG methylation was most prevalent in papillary RCC and least in VHL RCC. Many of the genes preferentially methylated in pRCC were linked to TGFbeta or ERK/Akt signalling. CONCLUSION: These findings demonstrate differing patterns of tumour-specific CpG methylation in VHL and non VHL clear cell RCC and papillary RCC, and identify multiple novel potential CpG methylation biomarkers for RCC.
dc.language.isoenen
dc.subjectKidney Canceren
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshCarcinoma, Renal Cell
dc.subject.meshCluster Analysis
dc.subject.meshCpG Islands
dc.subject.meshDNA Methylation
dc.subject.meshEpigenesis, Genetic
dc.subject.meshGene Regulatory Networks
dc.subject.meshHumans
dc.subject.meshKidney Neoplasms
dc.subject.meshMiddle Aged
dc.subject.meshPoisson Distribution
dc.subject.meshReproducibility of Results
dc.subject.meshStatistics, Nonparametric
dc.subject.meshvon Hippel-Lindau Disease
dc.titleCpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK. f.e.mcronald@bham.ac.uken
dc.identifier.journalMolecular Canceren
html.description.abstractBACKGROUND: Renal cell carcinoma (RCC) is histopathologically heterogeneous with clear cell and papillary the most common subtypes. The most frequent molecular abnormality in clear cell RCC is VHL inactivation but promoter methylation of tumour suppressor genes is common in both subtypes of RCC. To investigate whether RCC CpG methylation status was influenced by histopathology and VHL status we performed high-throughput epigenetic profiling using the Illumina Goldengate Methylation Array in 62 RCC (29 RCC from von Hippel-Lindau (VHL) disease patients, 20 sporadic clear cell RCC with wild type VHL and 13 sporadic papillary RCC). RESULTS: 43 genes were methylated in >20% of primary RCC (range 20-45%) and most (37/43) of these had not been reported previously to be methylated in RCC. The distribution of the number of methylated CpGs in individual tumours differed from the expected Poisson distribution (p < 0.00001; log-likelihood G test) suggesting that a subset of RCC displayed a CpG Island Methylator Phenotype. Comparison of RCC subtypes revealed that, on average, tumour specific CpG methylation was most prevalent in papillary RCC and least in VHL RCC. Many of the genes preferentially methylated in pRCC were linked to TGFbeta or ERK/Akt signalling. CONCLUSION: These findings demonstrate differing patterns of tumour-specific CpG methylation in VHL and non VHL clear cell RCC and papillary RCC, and identify multiple novel potential CpG methylation biomarkers for RCC.


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