CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma.
AuthorsMcRonald, Fiona E
Morris, Mark R
Clarke, Noel W
Brown, Michael D
Maher, Eamonn R
AffiliationCancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK. email@example.com
MetadataShow full item record
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.
CitationCpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma. 2009, 8:31 Mol. Cancer
- Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene and allelic losses at chromosome arm 3p in primary renal cell carcinoma: evidence for a VHL-independent pathway in clear cell renal tumourigenesis.
- Authors: Clifford SC, Prowse AH, Affara NA, Buys CH, Maher ER
- Issue date: 1998 Jul
- Epigenetic inactivation of the RASSF1A 3p21.3 tumor suppressor gene in both clear cell and papillary renal cell carcinoma.
- Authors: Morrissey C, Martinez A, Zatyka M, Agathanggelou A, Honorio S, Astuti D, Morgan NV, Moch H, Richards FM, Kishida T, Yao M, Schraml P, Latif F, Maher ER
- Issue date: 2001 Oct 1
- Von Hippel-Lindau (VHL) inactivation in sporadic clear cell renal cancer: associations with germline VHL polymorphisms and etiologic risk factors.
- Authors: Moore LE, Nickerson ML, Brennan P, Toro JR, Jaeger E, Rinsky J, Han SS, Zaridze D, Matveev V, Janout V, Kollarova H, Bencko V, Navratilova M, Szeszenia-Dabrowska N, Mates D, Schmidt LS, Lenz P, Karami S, Linehan WM, Merino M, Chanock S, Boffetta P, Chow WH, Waldman FM, Rothman N
- Issue date: 2011 Oct
- Unique molecular alteration patterns in von Hippel-Lindau (VHL) gene in a cohort of sporadic renal cell carcinoma patients from Pakistan.
- Authors: Khaliq S, Ajaz S, Firasat S, Shahid S, Hasan AS, Sultan G, Mohsin R, Hashmi A, Mubarak M, Naqvi SA, Rizvi SA, Mehdi SQ, Abid A
- Issue date: 2014 May-Jun
- Identification of cyclin D1 and other novel targets for the von Hippel-Lindau tumor suppressor gene by expression array analysis and investigation of cyclin D1 genotype as a modifier in von Hippel-Lindau disease.
- Authors: Zatyka M, da Silva NF, Clifford SC, Morris MR, Wiesener MS, Eckardt KU, Houlston RS, Richards FM, Latif F, Maher ER
- Issue date: 2002 Jul 1