Identification of Candidate Tumor Suppressor Genes Frequently Methylated in Renal Cell Carcinoma

Strategic Insights -

Researchers in the United Kingdom have made significant progress in understanding the causes of renal cell carcinoma, a type of kidney cancer. A study published in Oncogene identified eight genes that are frequently methylated in renal cell carcinoma, leading to the silencing of tumor suppressor genes. This epigenetic modification is a common cause of cancer inactivation in many types of human cancers.

Key Takeaways:

  • The study identified eight genes that are frequently methylated in renal cell carcinoma: BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1, and COL15A1.
  • These genes were selected for analysis using high-density gene expression microarrays in a functional epigenetic study of 11 renal cell carcinoma cell lines.
  • Eight genes showed frequent (30% of RCC tested) tumor-specific promoter region methylation, which was associated with transcriptional silencing.
  • Re-expression of BNC1, CST6, RPRM, and SFRP1 suppressed the growth of RCC cell lines, while RNA interference knock-down of BNC1, SFRP1, and COL14A1 increased the growth of RCC cell lines.
  • Methylation of BNC1 or COL14A1 was associated with a poorer prognosis independent of tumor size, stage, or grade.
  • The identification of these epigenetically inactivated candidate RCC TSGs can provide insights into renal tumorigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection.

Statistics:

  • 28 genes were selected for analysis of promoter methylation status in cell lines and primary RCC.
  • 8 genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1, and COL15A1) showed frequent (30%) tumor-specific promoter region methylation.
  • 11 renal cell carcinoma cell lines were used in the functional epigenetic study.
  • 70% of RCC tested showed hypermethylation of BNC1 or COL14A1.

Sources:

  • Morris, M. R., et al. (2010). Identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma. Oncogene, 29(14), 2104-2117.