Related Experiment Video
Updated: May 24, 2026

Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
Published on: October 15, 2018
Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation
1Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, PR China.
Abstract:
The TET (ten-eleven translocation) family of α-ketoglutarate (α-KG)-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. The TET2 gene is a bona fide tumor suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist of α-KG, linking 5mC oxidation to cancer development. We report here that the levels of 5hmC are dramatically reduced in human breast, liver, lung, pancreatic and prostate cancers when compared with the matched surrounding normal tissues. Associated with the 5hmC decrease is the substantial reduction of the expression of all three TET genes, revealing a possible mechanism for the reduced 5hmC in cancer cells. The decrease of 5hmC was also observed during tumor development in different genetically engineered mouse models. Together, our results identify 5hmC as a biomarker whose decrease is broadly and tightly associated with tumor development.
Insights
Levels of 5-hydroxymethylcytosine (5hmC) are significantly reduced in various human cancers. This decrease in 5hmC, linked to reduced ten-eleven translocation (TET) gene expression, serves as a potential biomarker for tumor development.
Area of Science:
- Epigenetics
- Cancer Biology
- Biochemistry
Background:
- Ten-eleven translocation (TET) enzymes regulate DNA demethylation via 5-methylcytosine (5mC) oxidation.
- TET2 is a tumor suppressor, and TET activity is linked to cancer via oncometabolites.
- 5-hydroxymethylcytosine (5hmC) is a key intermediate in DNA demethylation.
Purpose of the Study:
- To investigate the levels of 5hmC in human cancers.
- To explore the relationship between 5hmC levels and TET gene expression in tumors.
- To determine if 5hmC can serve as a biomarker for cancer development.
Main Methods:
- Quantification of 5hmC levels in various human cancer tissues and matched normal tissues.
- Analysis of TET gene expression in cancer samples.
- Observation of 5hmC changes in genetically engineered mouse models of cancer.
Main Results:
- 5hmC levels are dramatically reduced in human breast, liver, lung, pancreatic, and prostate cancers.
- A substantial decrease in the expression of all three TET genes accompanies the reduction in 5hmC.
- Reduced 5hmC levels were also observed during tumor progression in mouse models.
Conclusions:
- A significant decrease in 5hmC is broadly associated with human cancers.
- Reduced TET gene expression may explain the lower 5hmC levels in tumors.
- 5hmC is identified as a potential biomarker for tumor development.
More Related Videos
07:50Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina
Published on: August 29, 2018
06:07Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Related Concept Videos
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Abnormal Proliferation
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Replicative Cell Senescence
Epigenetic Regulation
X-chromosome...