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Updated: Jul 16, 2026
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Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins
K R Ostler1, E M Davis, S L Payne
1Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Oncogene
|March 14, 2007
Summary
Aberrant splicing of DNA methyltransferase 3B (DNMT3B) in cancer cells produces truncated proteins. These truncated DNMT3B variants may contribute to abnormal DNA methylation patterns observed in tumors.
Area of Science:
- Cancer Biology
- Epigenetics
- Molecular Oncology
Background:
- Cancer cells exhibit distinct DNA methylation patterns compared to normal cells.
- Hypermethylation of tumor suppressor genes and hypomethylation of repetitive DNA are characteristic of cancer.
- Mechanisms underlying aberrant DNA methylation in cancer remain largely unknown.
Purpose of the Study:
- To investigate the role of aberrant DNA methyltransferase 3B (DNMT3B) transcripts in cancer.
- To determine if truncated DNMT3B proteins can alter DNA methylation and gene expression.
Main Methods:
- Identification and characterization of DNMT3B transcripts in cancer cell lines and primary leukemia cells.
- Western blot analysis to detect truncated DNMT3B isoforms.
- Expression of DNMT3B7 in 293 cells followed by microarray analysis and CpG island methylation analysis.
Main Results:
- Over 20 aberrant DNMT3B transcripts, many retaining introns and encoding truncated proteins, were identified in cancer cells.
- Truncated DNMT3B isoforms were detected in nuclear extracts of cancer cells.
- Expression of DNMT3B7 led to altered gene expression and DNA methylation of CpG islands in 293 cells.
Conclusions:
- Aberrantly spliced DNMT3B transcripts producing truncated proteins are present in cancer cells.
- Truncated DNMT3B proteins have the potential to influence DNA methylation patterns and gene expression.
- These findings suggest a novel mechanism by which cancer cells establish abnormal DNA methylation profiles.
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