Related Experiment Video
Updated: Jul 20, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Comprehensive DNA methylation profiling in a human cancer genome identifies novel epigenetic targets
J M Ordway1, J A Bedell, R W Citek
1Orion Genomics, St Louis, MO 63108, USA.
Abstract:
Using a unique microarray platform for cytosine methylation profiling, the DNA methylation landscape of the human genome was monitored at more than 21,000 sites, including 79% of the annotated transcriptional start sites (TSS). Analysis of an oligodendroglioma derived cell line LN-18 revealed more than 4000 methylated TSS. The gene-centric analysis indicated a complex pattern of DNA methylation exists along each autosome, with a trend of increasing density approaching the telomeres. Remarkably, 2% of CpG islands (CGI) were densely methylated, and 17% had significant levels of 5 mC, whether or not they corresponded to a TSS. Substantial independent verification, obtained from 95 loci, suggested that this approach is capable of large scale detection of cytosine methylation with an accuracy approaching 90%. In addition, we detected large genomic domains that are also susceptible to DNA methylation reinforced inactivation, such as the HOX cluster on chromosome 7 (CH7). Extrapolation from the data suggests that more than 2000 genomic loci may be susceptible to methylation and associated inactivation, and most have yet to be identified. Finally, we report six new targets of epigenetic inactivation (IRX3, WNT10A, WNT6, RARalpha, BMP7 and ZGPAT). These targets displayed cell line and tumor specific differential methylation when compared with normal brain samples, suggesting they may have utility as biomarkers. Uniquely, hypermethylation of the CGI within an IRX3 exon was correlated with over-expression of IRX3 in tumor tissues and cell lines relative to normal brain samples.
Insights
This study maps human genome DNA methylation at over 21,000 sites, revealing complex patterns and identifying new epigenetic targets for cancer biomarkers. The findings highlight methylation
Area of Science:
- Epigenetics
- Genomics
- Cancer Biology
Background:
- DNA methylation is crucial for gene regulation.
- Understanding the human genome's methylation landscape is key to disease research.
- Previous profiling methods lacked comprehensive coverage.
Purpose of the Study:
- To comprehensively profile the human genome's DNA methylation landscape.
- To identify novel targets of epigenetic inactivation.
- To explore the utility of these targets as cancer biomarkers.
Main Methods:
- Utilized a unique microarray platform for cytosine methylation profiling.
- Analyzed over 21,000 genomic sites, including 79% of annotated transcriptional start sites (TSS).
- Performed gene-centric analysis and independent verification of methylation detection.
Main Results:
- Identified over 4000 methylated TSS in an oligodendroglioma cell line.
- Observed a trend of increasing methylation density towards telomeres.
- Detected methylation in 2% of CpG islands (CGI) and significant levels in 17%.
- Identified large genomic domains, like the HOX cluster, susceptible to methylation-induced inactivation.
- Reported six new epigenetic inactivation targets (IRX3, WNT10A, WNT6, RARalpha, BMP7, ZGPAT).
- Found cell line and tumor-specific differential methylation for these targets compared to normal brain samples.
- Correlated hypermethylation of an IRX3 CGI with its overexpression in tumors.
Conclusions:
- The developed microarray platform enables large-scale, accurate DNA methylation profiling.
- The human genome exhibits a complex methylation pattern with implications for gene regulation.
- Newly identified epigenetic targets may serve as valuable biomarkers for cell line and tumor-specific diagnostics.
- Further research is needed to identify the >2000 potential methylation-susceptible genomic loci.
Related Concept Videos
01:37Epigenetic Regulation
X-chromosome...
01:46Epigenetic Regulation