title: TET proteins and the control of cytosine demethylation in cancer.
abstract: The discovery that ten-eleven translocation (TET) proteins are α-ketoglutarate-dependent dioxygenases involved in the conversion of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine and 5-carboxycytosine has revealed new pathways in the cytosine methylation and demethylation process. The description of inactivating mutations in TET2 suggests that cellular transformation is in part caused by the deregulation of this 5-mC conversion. The direct and indirect deregulation of methylation control through mutations in DNA methyltransferase and isocitrate dehydrogenase (IDH) genes, respectively, along with the importance of cytosine methylation in the control of normal and malignant cellular differentiation have provided a conceptual framework for understanding the early steps in cancer development. Here, we review recent advances in our understanding of the cytosine methylation cycle and its implication in cellular transformation, with an emphasis on TET enzymes and 5-hmC. Ongoing clinical trials targeting the activity of mutated IDH enzymes provide a proof of principle that DNA methylation is targetable, and will trigger further therapeutic applications aimed at controlling both early and late stages of cancer development.
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1170, équipe labellisée Ligue Contre le Cancer, 94805 Villejuif, France ; Institut Gustave Roussy, 94805 Villejuif, France ; University Paris 11 Sud, 91405 Orsay, France.
authors: Laurianne
authors: L
authors: Scourzic
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1170, équipe labellisée Ligue Contre le Cancer, 94805 Villejuif, France ; Institut Gustave Roussy, 94805 Villejuif, France ; University Paris 11 Sud, 91405 Orsay, France.
authors: Enguerran
authors: E
authors: Mouly
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1170, équipe labellisée Ligue Contre le Cancer, 94805 Villejuif, France ; Institut Gustave Roussy, 94805 Villejuif, France ; University Paris 11 Sud, 91405 Orsay, France.
authors: Olivier A
authors: OA
authors: Bernard
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