Related Experiment Video
Updated: Apr 6, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Role of DNA methylation in renal cell carcinoma
Niraj Shenoy1, Nishanth Vallumsetla2, Yiyu Zou3
1Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10467, USA. knirajshenoy@gmail.com.
Abstract:
Alterations in DNA methylation are seen in cancers and have also been examined in clear cell renal cell carcinoma (ccRCC). Numerous tumor suppressor genes have been reported to be partially or completely silenced due to hypermethylation of their promoters in single-locus studies, and the use of hypomethylating agents has been shown to restore the expression of many of these genes in vitro. In particular, members of the Wnt and TGF-beta pathways, pro-apoptotic genes such as APAF-1 and negative cell-cycle regulators such as KILLIN have been shown to be epigenetically silenced in numerous studies in ccRCC. Recently, TCGA analysis of a large cohort of ccRCC samples demonstrated that aberrant hypermethylation correlated with the stage and grade in kidney cancer. Our genome-wide studies also revealed aberrant widespread hypermethylation that affected regulatory regions of the kidney genome in ccRCC. We also observed that aberrant enhancer hypermethylation was predictive of adverse prognosis in ccRCC. Recent discovery of mutations affecting epigenetic regulators reinforces the importance of these changes in the pathophysiology of ccRCC and points to the potential of epigenetic modulators in the treatment of this malignancy.
Insights
Aberrant DNA methylation patterns are prevalent in clear cell renal cell carcinoma (ccRCC), impacting tumor suppressor genes and predicting adverse prognosis. Epigenetic alterations are crucial in ccRCC development and suggest potential therapeutic targets.
Area of Science:
- Oncology
- Epigenetics
- Genomics
Background:
- DNA methylation alterations are hallmarks of cancer, including clear cell renal cell carcinoma (ccRCC).
- Previous studies identified promoter hypermethylation silencing tumor suppressor genes (e.g., Wnt, TGF-beta pathway members, APAF-1, KILLIN) in ccRCC.
- Aberrant hypermethylation has been linked to tumor stage and grade in kidney cancer.
Purpose of the Study:
- To investigate genome-wide DNA methylation patterns in ccRCC.
- To determine the prognostic significance of aberrant enhancer hypermethylation in ccRCC.
- To highlight the role of epigenetic dysregulation in ccRCC pathophysiology and treatment.
Main Methods:
- Genome-wide methylation profiling of ccRCC samples.
- Analysis of The Cancer Genome Atlas (TCGA) data for ccRCC cohort.
- Correlation analysis between methylation patterns, clinical stage, grade, and patient prognosis.
Main Results:
- Genome-wide studies revealed widespread aberrant hypermethylation in regulatory regions of the kidney genome in ccRCC.
- Aberrant enhancer hypermethylation was identified as a predictor of adverse prognosis in ccRCC.
- TCGA analysis confirmed correlation between aberrant hypermethylation and ccRCC stage/grade.
Conclusions:
- Aberrant DNA hypermethylation, particularly in enhancers, is a significant feature of ccRCC and predicts poor outcomes.
- Epigenetic dysregulation is integral to ccRCC pathophysiology.
- Epigenetic modulators represent a promising therapeutic avenue for ccRCC treatment.
Related Concept Videos
Epigenetic Regulation
Epigenetic Regulation
X-chromosome...
Phase II Reactions: Methylation Reactions
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...

