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Updated: Jun 6, 2026
06:07
Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression
Ashraf E K Ibrahim1, Mark J Arends, Ana-Luisa Silva
1Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, UK. aeki2@cam.ac.uk
Gut
|November 12, 2010
Summary
Epigenetic changes in colorectal cancer progression are locus-dependent and linked to increased DNA methyltransferase 3B (DNMT3B) expression, suggesting a causal role in tumor development.
Area of Science:
- Epigenetics
- Molecular Oncology
- Gastroenterology
Background:
- Aberrant gene methylation is implicated in colorectal neoplasia progression.
- Previous studies lacked model-based analysis of incremental methylation changes through adenoma stages.
- Biological drivers of these methylation changes remain undefined.
Purpose of the Study:
- To analyze the onset and patterns of methylation changes in key genes during colorectal neoplastic progression.
- To correlate these methylation changes with DNA methyltransferase 3B (DNMT3B) expression levels.
- To define the biological drivers of methylation changes in colorectal neoplasia.
Main Methods:
- Linear mixed-effects modeling was used to analyze methylation patterns.
- Quantitative pyrosequencing assays measured methylation in 261 tissue samples.
- Immunohistochemical analysis assessed DNMT3B expression in a subset of 64 cases.
Main Results:
- Methylation changes during colorectal neoplastic progression are locus-dependent.
- RUNX3, NEUROG1, and CACNA1G showed early methylation changes, while SFRP2 and IGF2 DMR0 changed at the adenomatous stage.
- DNMT3B expression increased significantly and correlated with specific methylation patterns.
Conclusions:
- Hierarchical epigenetic alterations occur at transition points in colorectal neoplastic progression.
- Cumulative methylation changes correlate with increased DNMT3B expression.
- A causal relationship between DNMT3B expression and epigenetic alterations is suggested.
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