Related Experiment Video
Updated: Jun 16, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
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.
Abstract:
Promoter region hyermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many types of human cancers. Functional epigenetic studies, in which gene expression is induced by treatment with demethylating agents, may identify novel genes with tumour-specific methylation. We used high-density gene expression microarrays in a functional epigenetic study of 11 renal cell carcinoma (RCC) cell lines. Twenty-eight genes were then selected for analysis of promoter methylation status in cell lines and primary RCC. Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1 and COL15A1) showed frequent (>30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing. Re-expression of BNC1, CST6, RPRM and SFRP1 suppressed the growth of RCC cell lines and 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 tumour size, stage or grade. The identification of these epigenetically inactivated candidate RCC TSGs can provide insights into renal tumourigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection.
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.
Related Concept Videos
Epigenetic Regulation
Epigenetic Regulation
X-chromosome...
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
