The link between epigenetics and cancer

Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Epigenetic modifications play a fundamental role in the regulation of processes such as transcription, DNA repair, and replication. Alterations of genes regulating epigenetic processes are frequently found as cancer drivers and may be caused by changes in DNA and RNA modifications, histone modifications, and nucleosome remodeling. Abnormal gene expression patterns can lead to the initiation and maintenance of various cancers.

Whole-genome sequencing studies demonstrated the presence of recurrent somatic mutations in numerous epigenetic regulators in various types of cancer^1,2. Histone modifications such as acetylation and methylation are among the most widely affected epigenetic pathways in cancer. For example, mutations in a histone demethylase UTX (KDM6A) are shown in up to 12 histologically distinct cancers³.

The reversible nature of epigenetic modifications has led to the emergence of the promising field of epigenetic therapy. Multiple small-molecule epigenetic inhibitors are being developed for use in cancer therapies. Three of these inhibitors, targeting DNMTs, HDACs, and JAK2, have already gained approval by the US Food and Drug Administration (FDA).

References

1. Forbes, S. A., et al. COSMICL mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer Nucleic Acids Res 39 ,945-950 (2011)
2. Stratton, M. R., Campbell, P. J., Futreal, P. A. The cancer genome Nature 458 ,719-724 (2009)
3. van Haaften, G., et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer Nat. Genet. 41 ,521-523 (2009)