CEMdb

The essential role of epigenetics in various cellular processes of normal and cancerous cells has drawn considerable attentions in recent years. It has been reported that the selective expression of gene resulted due to epigenetic modifications, were instrumental in deciding the fate of proteins involved in binding of chromatin & the related machinery of transcription. These findings had revealed critical infection related epigenetic components and pathways which are crucial for discovery of novel therapeutics. A major fraction of such reported cases comprised of epigenetic misregulation related to human cancer. Cancer epigenetics is the investigation of epigenetic alterations to the genome of tumor cells that don't essentially include a change or variation in the nucleotide succession.

The earliest indications of an epigenetic connection to cancer were resultant of various studies on gene expression and methylation of DNA. The quantum of such studies was well discussed elsewhere in a survey article by Feinberg enumerating the historical backdrop of growth of epigenetics. The International Cancer Genome Consortium (ICGC) has significantly strengthened these early observations. The whole genome sequencing in an immeasurable cluster of cancers has given an index of recurrent somatic mutations in several epigenetic controllers. Epigenetic data is contained in the cell in various forms that incorporate methylation of DNA, modification of histones (methylation, phosphorylation, acetylation, and so forth.), positioning of nucleosome and microRNA expression, these data together constitutes the epigenome. All these modifications in the chromatin structure lead to the activation or silencing of the expression of genes. Although an exhaustive understanding of epigenomic dysregulation in specific type of cancer has not been clarified yet, there exists a comprehension of tumor-specific types of modification which occurs in human cancer. The remodeling of chromatin is carried out with the help of two important mechanisms; the cytosine residues methylation in DNA and an array of post-translational modifications (PTMs) occurring at the N-terminal ends of histone proteins. These PTMs comprise of methylation, acetylation, ubiquitylation, phosphorylation, glycosylation, sumoylation, ADP-ribosylation, citrullination, biotinylation and carbonylation. Among all such PTMs the lysine amino acid residues of histone tails are reported to be methylated, acetylated or ubiquitilated; also the arginine amino acid residues are found to be methylated; whereas threonine & serine amino acid residues were seen to undergo phosphorylation. These covalent alterations have the propensity to bring cross-talk, which is known as the histone code that can be positively or negatively associated with specific states of transcription or chromatin organization.

Human tumors are considered fundamentally to be a disease of genetic level, where several genes get mutated or abnormally proliferated during the formation of cancer. In fact, all the various cellular pathways contributing to the neoplastic phenotype are affected by epigenetic genes in cancer. They are being investigated as biomarkers in clinical use for early detection of disease, tumor classification and response to treatment with classical chemotherapy agents, target compounds & epigenetic drugs. These sorts of subtle adjustments are fundamental for ordinary cell physiology and function, aiding in the initiation or restraint of essential qualities in different phases of advancement. There are occurrences, however, in which the changes can be modified to actuate sporadic transcription of gene. In these cases, the results can incite different types of tumors in human, with two key zones of modification viz. methylation of DNA sequences, and changes on the histones encompassing DNA. Since the disclosure of their association in the change of expression of the gene, modification of histones and methylation of DNA have been involved in sicknesses other than malignancy. One paramount part of epigenetic methylation is its reversibility; this key property has made a guaranteeing field of epigenetic treatment, which has prompted the improvement of a few FDA sanction drugs for treatment of tumors. It has likewise produced a few new and energizing thoughts for future ways of treatment.

REFERENCES

1. 1. Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4: 143–153
2. 2. Forbes SA, Bindal N, Bamford S, Cole C, Kok CY, Beare D, Jia M, Shepherd R, Leung K, Menzies A, et al (2011) COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 39 (Database issue): D945–D950
3. 3. Stratton MR, Campbel PJ, Futreal PA (2009) The cancer genome. Nature 458: 719–724
4. 4. Campbell RM, Tummino PJ (2014) Cancer epigenetics drug discovery and development: the challenge of hitting the mark. The Journal of clinical investigation 124(1): 64-69
5. 5. Herceg Z, Ushijima T (2010) Introduction: epigenetics and cancer. Advances in genetics 70: 1-23
6. 6. Baylin SB (2008) Epigenetics and Cancer. The Molecular Basis of Cancer pp. 57–65
7. 7. Jones P a, Baylin SB (2007) The epigenomics Cancer. Cell 128(4): 683–92
8. 8. Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4): 693–705
9. 9. Kelly TK, De Carvalho DD, Jones P a (2010) Epigenetic modifications as therapeutic targets. Nature Biotechnol 28(10):1069–78
10. 10. Baylin SB, Jones PA (2011) A decade of exploring the cancer epigenome — biological and translational implications. Nat Rev Cancer 11(10): 726–734