Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation

H Yang1, Y Liu, F Bai

  • 1Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, PR China.

Oncogene
|March 7, 2012
PubMed

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.

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