Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma

Article, Other literature type English OPEN
Ricketts, Christopher J ; Morris, Mark R ; Gentle, Dean ; Brown, Michael ; Wake, Naomi ; Woodward, Emma R ; Clarke, Noel ; Latif, Farida ; Maher, Eamonn R (2012)
  • Publisher: Landes Bioscience
  • Related identifiers: doi: 10.4161/epi.7.3.19103
  • Subject: Molecular Biology | RCC | Methylation | Renal cell carcinoma (RCC) | /dk/atira/pure/subjectarea/asjc/1300/1312 | Renal Cancer | /dk/atira/pure/subjectarea/asjc/1300/1306 | Research Paper | Epigenetics | Cancer Research
    mesheuropmc: urologic and male genital diseases

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.
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