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CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma
McRonald, FE Morris, MR Gentle, D Winchester, L Baban, D Ragoussis, J Clarke, NW Brown, MD Kishida, T Yao, M
McRonald, FE
Morris, MR
Gentle, D
Winchester, L
Baban, D
Ragoussis, J
Clarke, NW
Brown, MD
Kishida, T
Yao, M
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Other contributors
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Epub Date
Issue Date
2009-06-03
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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. © 2009 McRonald et al; licensee BioMed Central Ltd.
Citation
McRonald, F. E., Morris, M. R., Gentle, D., Winchester, L., Baban, D., Ragoussis, J., Clarke, N. W., Brown, M. D., Kishida, T., Yao, M., Latif, F. and Maher, E. R. (2009) CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma, Molecular Cancer (2009), 8, 31.
Publisher
Journal
Research Unit
PubMed ID
19493342
PubMed Central ID
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Journal article
Language
en
Description
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ISSN
EISSN
1476-4598
ISBN
ISMN
Gov't Doc #
Sponsors
Cancer Research UK
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Licence for published version: Creative Commons Attribution 4.0 International