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Updated: Mar 7, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Pan-cancer analysis of frequent DNA co-methylation patterns reveals consistent epigenetic landscape changes in
1Department of Biomedical Informatics, The Ohio State University, Columbus, OH, 43210, USA.
Background:
DNA methylation is the major form of epigenetic modifications through which the cell regulates the gene expression and silencing. There have been extensive studies on the roles of DNA methylation in cancers, and several cancer drugs were developed targeting this process. However, DNA co-methylation cluster has not been examined in depth, and co-methylation in multiple cancer types has never been studied previously.
Results:
In this study, we applied newly developed lmQCM algorithm to mine co-methylation clusters using methylome data from 11 cancer types in TCGA database, and found frequent co-methylated gene clusters exist in these cancer types. Among the four identified frequent clusters, two of them separate the tumor sample from normal sample in 10 out of 11 cancer types, which indicates that consistent epigenetic landscape changes exist in multiple cancer types.
Conclusion:
This discovery provides new insight on the epigenetic regulation in cancers and leads to potential new direction for epigenetic biomarker and cancer drug discovery. We also found that genes commonly believed to be silenced via hypermethylation in cancers may still display highly variable methylation levels among cancer cells, and should be considered while using them as epigenetic biomarkers.
Insights
DNA methylation patterns, or epigenetic modifications, were analyzed across 11 cancer types. Frequent co-methylation clusters were identified, with two clusters distinguishing tumor from normal samples, revealing consistent epigenetic changes in cancer.
Area of Science:
- Epigenetics
- Cancer Biology
- Genomics
Background:
- DNA methylation is a key epigenetic mechanism regulating gene expression and silencing.
- While DNA methylation's role in cancer is studied, co-methylation clusters across multiple cancer types remain underexplored.
Purpose of the Study:
- To investigate the existence and characteristics of DNA co-methylation clusters in diverse cancer types.
- To identify potential epigenetic biomarkers and therapeutic targets through co-methylation analysis.
Main Methods:
- Utilized the novel lmQCM algorithm for co-methylation cluster mining.
- Analyzed methylome data from 11 cancer types obtained from The Cancer Genome Atlas (TCGA) database.
Main Results:
- Identified frequent co-methylated gene clusters across the analyzed cancer types.
- Discovered two specific clusters that effectively differentiate tumor samples from normal samples in 10 out of 11 cancer types.
- Observed that genes often considered silenced by hypermethylation can exhibit variable methylation levels in cancer cells.
Conclusions:
- Consistent epigenetic landscape alterations occur across multiple cancer types.
- Co-methylation analysis offers novel insights into epigenetic regulation in cancer.
- Findings suggest potential for new epigenetic biomarkers and cancer drug development, with a note of caution regarding methylation variability.
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