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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, Latif F, Maher ER - Mol. Cancer (2009)

Bottom Line: 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). 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.Many of the genes preferentially methylated in pRCC were linked to TGFbeta or ERK/Akt signalling.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK. f.e.mcronald@bham.ac.uk

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.

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Genes that were methylated in all normal kidney tumour samples (N = 6) but methylated in <72% of renal tumours analysed: comparison of frequency of methylation in different tumour types.
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Figure 3: Genes that were methylated in all normal kidney tumour samples (N = 6) but methylated in <72% of renal tumours analysed: comparison of frequency of methylation in different tumour types.

Mentions: 18 genes were methylated in all six normal kidney tissue samples but in <72% of renal tumours analysed: CARD15 (18% of tumours), HLA-DRA (24%), SPARC (34%), IL8 (35%), SEPT9 (39%), HLA-DPB1 (45%), TNFSF10 (47%), VAMP8 (50%), PRKCDBP (55%), HLA-DPA1 (56%), HDAC1 (58%), BTK (58%), S100A2 (60%), MPO (61%), CRK (61%), CAPG (61%), NEU1 (69%), ELL (71%). There was no consistent pattern in the frequency of methylation loss in the different subtypes of renal tumours (Figure 3).


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, Latif F, Maher ER - Mol. Cancer (2009)

Genes that were methylated in all normal kidney tumour samples (N = 6) but methylated in <72% of renal tumours analysed: comparison of frequency of methylation in different tumour types.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698845&req=5

Figure 3: Genes that were methylated in all normal kidney tumour samples (N = 6) but methylated in <72% of renal tumours analysed: comparison of frequency of methylation in different tumour types.
Mentions: 18 genes were methylated in all six normal kidney tissue samples but in <72% of renal tumours analysed: CARD15 (18% of tumours), HLA-DRA (24%), SPARC (34%), IL8 (35%), SEPT9 (39%), HLA-DPB1 (45%), TNFSF10 (47%), VAMP8 (50%), PRKCDBP (55%), HLA-DPA1 (56%), HDAC1 (58%), BTK (58%), S100A2 (60%), MPO (61%), CRK (61%), CAPG (61%), NEU1 (69%), ELL (71%). There was no consistent pattern in the frequency of methylation loss in the different subtypes of renal tumours (Figure 3).

Bottom Line: 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). 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.Many of the genes preferentially methylated in pRCC were linked to TGFbeta or ERK/Akt signalling.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK. f.e.mcronald@bham.ac.uk

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.

Show MeSH
Related in: MedlinePlus