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Updated: Jan 20, 2026
Methylated DNA Immunoprecipitation
Published on: January 2, 2009
Genes Controlled by DNA Methylation Are Involved in Wilms Tumor Progression
João Victor da Silva Guerra1,2, Bruna Maria de Sá Pereira3, Jéssica Gonçalves Vieira da Cruz4
1Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas 13083-970, Brazil.
Abstract:
To identify underlying mechanisms involved with metastasis formation in Wilms tumors (WTs), we performed comprehensive DNA methylation and gene expression analyses of matched normal kidney (NK), WT blastemal component, and metastatic tissues (MT) from patients treated under SIOP 2001 protocol. A linear Bayesian framework model identified 497 differentially methylated positions (DMPs) between groups that discriminated NK from WT, but MT samples were divided in two groups. Accordingly, methylation variance grouped NK and three MT samples tightly together and all WT with four MT samples that showed high variability. WT were hypomethylated compared to NK, and MT had a hypermethylated pattern compared to both groups. The methylation patterns were in agreement with methylases and demethylases expression. Methylation data pointed to the existence of two groups of metastases. While hierarchical clustering analysis based on the expression of all 2569 differentially expressed genes (DEGs) discriminated WT and MT from all NK samples, the hierarchical clustering based on the expression of 44 genes with a differentially methylated region (DMR) located in their promoter region revealed two groups: one containing all NKs and three MTs and one containing all WT and four MTs. Methylation changes might be controlling expression of genes associated with WT progression. The 44 genes are candidates to be further explored as a signature for metastasis formation in WT.
Insights
DNA methylation analysis reveals distinct patterns in Wilms tumor (WT) metastasis. These findings identify potential gene signatures for understanding WT progression and metastasis formation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Wilms tumors (WTs) are pediatric kidney cancers.
- Metastasis formation is a critical factor in WT prognosis.
- Understanding the molecular mechanisms of WT metastasis is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the underlying mechanisms of metastasis formation in Wilms tumors.
- To identify molecular differences between normal kidney, Wilms tumor, and metastatic tissues.
- To explore potential gene signatures associated with WT metastasis.
Main Methods:
- Comprehensive DNA methylation and gene expression analyses were performed on matched normal kidney (NK), WT blastemal component, and metastatic tissues (MT).
- A linear Bayesian framework model was used to identify differentially methylated positions (DMPs).
- Hierarchical clustering analysis was applied to gene expression data.
Main Results:
- 497 DMPs were identified, discriminating NK from WT, with MT samples dividing into two distinct groups.
- WT tissues showed hypomethylation compared to NK, while MT tissues exhibited hypermethylation.
- Gene expression analysis revealed two distinct groups of metastases, with 44 candidate genes identified for potential metastasis signature.
Conclusions:
- DNA methylation patterns correlate with gene expression and may control genes involved in Wilms tumor progression.
- Distinct methylation and expression profiles exist between normal kidney, primary WT, and metastatic tissues.
- A panel of 44 genes shows promise as a signature for predicting metastasis formation in Wilms tumors.
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