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    CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma.

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    Authors
    McRonald, Fiona E
    Morris, Mark R
    Gentle, Dean
    Winchester, Laura
    Baban, Dilair
    Ragoussis, Jiannis
    Clarke, Noel W
    Brown, Michael D
    Kishida, Takeshi
    Yao, Masahiro
    Latif, Farida
    Maher, Eamonn R
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    Affiliation
    Cancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK. f.e.mcronald@bham.ac.uk
    Issue Date
    2009
    
    Metadata
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    Abstract
    BACKGROUND: 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.
    Citation
    CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma. 2009, 8:31 Mol. Cancer
    Journal
    Molecular Cancer
    URI
    http://hdl.handle.net/10541/85374
    DOI
    10.1186/1476-4598-8-31
    PubMed ID
    19493342
    Type
    Article
    Language
    en
    ISSN
    1476-4598
    ae974a485f413a2113503eed53cd6c53
    10.1186/1476-4598-8-31
    Scopus Count
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research
    Clinical Oncology
    Urological Oncology

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