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Identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma

M R Morris1, C Ricketts, D Gentle

  • 1Cancer Research UK Renal Molecular Oncology Group, University of Birmingham, Birmingham, UK.

Oncogene
|February 16, 2010
PubMed

Insights

Epigenetic silencing of tumor suppressor genes (TSGs) is common in cancer. This study identified novel TSGs in renal cell carcinoma (RCC) through functional epigenetic analysis, revealing potential therapeutic targets and biomarkers.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Promoter hypermethylation and transcriptional silencing frequently inactivate tumor suppressor genes (TSGs) in human cancers.
  • Functional epigenetic studies using demethylating agents can identify novel genes with tumor-specific methylation patterns.

Purpose of the Study:

  • To identify novel epigenetically inactivated tumor suppressor genes (TSGs) in renal cell carcinoma (RCC).
  • To analyze the methylation status and functional impact of candidate TSGs in RCC.
  • To investigate the prognostic significance of identified TSGs in RCC patients.

Main Methods:

  • High-density gene expression microarrays were employed in a functional epigenetic study of 11 RCC cell lines.
  • Promoter methylation status of selected genes was analyzed in RCC cell lines and primary tumors.
  • Gene re-expression and RNA interference (RNAi) knock-down experiments were performed to assess functional effects on RCC cell growth.

Main Results:

  • Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1, COL15A1) exhibited frequent (>30%) tumor-specific promoter region methylation in RCC.
  • Hypermethylation of these genes was associated with transcriptional silencing.
  • Re-expression of BNC1, CST6, RPRM, and SFRP1 suppressed RCC cell growth, while RNAi knock-down of BNC1, SFRP1, and COL14A1 increased RCC cell growth.
  • Methylation of BNC1 or COL14A1 correlated with poorer prognosis, independent of tumor characteristics.

Conclusions:

  • The study identified several epigenetically inactivated candidate RCC TSGs.
  • These findings offer insights into renal tumorigenesis and provide a basis for novel therapeutic strategies and biomarkers for RCC prognosis and detection.

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