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Trends Genet. 2014 Oct;30(10):464-74. doi: 10.1016/j.tig.2014.07.005. Epub 2014 Aug 14.

Connections between TET proteins and aberrant DNA modification in cancer.

Author information

1
La Jolla Institute, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA. Electronic address: yun.huang@ibt.tamhsc.edu.
2
La Jolla Institute, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA. Electronic address: arao@liai.org.

Abstract

DNA methylation has been linked to aberrant silencing of tumor suppressor genes in cancer, and an imbalance in DNA methylation-demethylation cycles is intimately implicated in the onset and progression of tumors. Ten-eleven translocation (TET) proteins are Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenases that successively oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), thereby mediating active DNA demethylation. In this review, we focus on the pathophysiological role of TET proteins and 5hmC in cancer. We present an overview of loss-of-function mutations and abnormal expression and regulation of TET proteins in hematological malignancies and solid tumors, and discuss the potential prognostic value of assessing TET mutations and 5hmC levels in cancer patients. We also address the crosstalk between TET and two critical enzymes involved in cell metabolism: O-linked β-N-acetylglucosamine transferase (OGT) and isocitrate dehydrogenase (IDH). Lastly, we discuss the therapeutic potential of targeting TET proteins and aberrant DNA methylation in cancer.

KEYWORDS:

5-hydroxymethylcytosine; 5hmC; 5mC; DNA demethylation; DNA methylation; IDH; OGT; TET; cancer

PMID:
25132561
PMCID:
PMC4337960
DOI:
10.1016/j.tig.2014.07.005
[Indexed for MEDLINE]
Free PMC Article

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