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Review
. 2017 Sep;7(9):170152.
doi: 10.1098/rsob.170152.

Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: an update

Pere Llinàs-Arias  1 , Manel Esteller  2   3   4
Affiliations
Review

Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: an update

Pere Llinàs-Arias et al. Open Biol. 2017 Sep.

Abstract

Cancer cells undergo many different alterations during their transformation, including genetic and epigenetic events. The controlled division of healthy cells can be impaired through the downregulation of tumour suppressor genes. Here, we provide an update of the mechanisms in which epigenetically altered coding and non-coding tumour suppressor genes are implicated. We will highlight the importance of epigenetics in the different molecular pathways that lead to enhanced and unlimited capacity of division, genomic instability, metabolic shift, acquisition of mesenchymal features that lead to metastasis, and tumour plasticity. We will briefly describe these pathways, focusing especially on genes whose epigenetic inactivation through DNA methylation has been recently described, as well as on those that are well established as being epigenetically silenced in cancer. A brief perspective of current clinical therapeutic approaches that can revert epigenetic inactivation of non-coding tumour suppressor genes will also be given.

Keywords: cancer; epigenetics; inactivation; methylation.

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Conflict of interest statement

The authors have no relevant competing interests.

Figures

Figure 1.
Figure 1.
Covalent mechanisms of epigenetic regulation. DNA is bound to histone proteins forming the nucleosomes. Nucleosome compaction depends on histone tail modification, which is regulated by histone writers, readers and erasers. DNA methylation in CpG dinucleotides is regulated by different enzymes. DNMT1 and DNMT3a mediate the 5′mC synthesis. TET proteins catalyse DNA demethylation.
Figure 2.
Figure 2.
Molecular pathways altered by epigenetic inactivation in cancer. Represented pathways are altered in cancer. Red proteins correspond to epigenetically silenced genes.
See this image and copyright information in PMC

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