Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma
Autor: | Emma R. Woodward, Eamonn R. Maher, Michael D Brown, Farida Latif, Dean Gentle, Christopher J. Ricketts, Noel W. Clarke, Naomi C. Wake, Mark R. Morris |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Cancer Research
Biology urologic and male genital diseases Methylation RNA interference Cell Line Tumor Tumor Cells Cultured Cluster Analysis Humans Gene silencing Epigenetics Carcinoma Renal Cell Gene Molecular Biology Gene knockdown Renal cell carcinoma (RCC) DNA Methylation Molecular biology RCC Kidney Neoplasms HEK293 Cells Genes CpG site Renal Cancer DNA methylation CpG Islands Sequence Analysis Research Paper |
Zdroj: | Ricketts, C J, Morris, M R, Gentle, D, Brown, M, Wake, N, Woodward, E R, Clarke, N, Latif, F & Maher, E R 2012, ' Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma ', Epigenetics : official journal of the DNA Methylation Society, vol. 7, no. 3, pp. 278-290 . https://doi.org/10.4161/epi.7.3.19103 Ricketts, C J, Morris, M R, Gentle, D, Brown, M, Wake, N, Woodward, E R, Clarke, N, Latif, F & Maher, E R 2012, ' Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma ', Epigenetics: official journal of the DNA Methylation Society, vol. 7, no. 3, pp. 278-290 . https://doi.org/10.4161/epi.7.3.19103 |
Popis: | In order to identify novel candidate tumor suppressor genes (TSGs) implicated in renal cell carcinoma (RCC), we performed genome-wide methylation profiling of RCC using the HumanMethylation27 BeadChips to assess methylation at >14,000 genes. Two hundred and twenty hypermethylated probes representing 205 loci/genes were identified in genomic CpG islands. A subset of TSGs investigated in detail exhibited frequent tumor methylation, promoter methylation associated transcriptional silencing and reactivation after demethylation in RCC cell lines and downregulation of expression in tumor tissue (e.g., SLC34A2 specifically methylated in 63% of RCC, OVOL1 in 40%, DLEC1 in 20%, TMPRSS2 in 26%, SST in 31% and BMP4 in 35%). As OVOL1, a putative regulator of c-Myc transcription, and SST (somatostatin) had not previously been linked to cancer and RCC, respectively, we (1) investigated their potential relevance to tumor growth by RNAi knockdown and found significantly increased anchorage-independent growth and (2) demonstrated that OVOL1 knockdown increased c-Myc mRNA levels. © 2012 Landes Bioscience. |
Databáze: | OpenAIRE |
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