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Molecular Cancer
Published in: Molecular Cancer 1/2009

Open Access 01-12-2009 | Research

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

Authors: Fiona E McRonald, Mark R Morris, Dean Gentle, Laura Winchester, Dilair Baban, Jiannis Ragoussis, Noel W Clarke, Michael D Brown, Takeshi Kishida, Masahiro Yao, Farida Latif, Eamonn R Maher

Published in: Molecular Cancer | Issue 1/2009

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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 TGFβ 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.
Appendix
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Metadata
Title
CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma
Authors
Fiona E McRonald
Mark R Morris
Dean Gentle
Laura Winchester
Dilair Baban
Jiannis Ragoussis
Noel W Clarke
Michael D Brown
Takeshi Kishida
Masahiro Yao
Farida Latif
Eamonn R Maher
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2009
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-8-31

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