Cancer epigenetics

Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development.[1] They may be just as important, if not even more important, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing (caused by epigenetic promoter hypermethylation of CpG islands) than by mutations. As Vogelstein et al. points out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations.[2] However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in the promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa.[3][4][5] Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy.[6][7] In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as the silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. There are several medications which have epigenetic impact, that are now used in a number of these diseases.

Epigenetics patterns in a normal and cancer cells
Epigenetic alterations in tumour progression
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  2. ^ Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW (March 2013). "Cancer genome landscapes". Science. 339 (6127): 1546–1558. Bibcode:2013Sci...339.1546V. doi:10.1126/science.1235122. PMC 3749880. PMID 23539594.
  3. ^ Illingworth RS, Gruenewald-Schneider U, Webb S, Kerr AR, James KD, Turner DJ, et al. (September 2010). "Orphan CpG islands identify numerous conserved promoters in the mammalian genome". PLOS Genetics. 6 (9): e1001134. doi:10.1371/journal.pgen.1001134. PMC 2944787. PMID 20885785.
  4. ^ Wei J, Li G, Dang S, Zhou Y, Zeng K, Liu M (2016). "Discovery and Validation of Hypermethylated Markers for Colorectal Cancer". Disease Markers. 2016: 2192853. doi:10.1155/2016/2192853. PMC 4963574. PMID 27493446.
  5. ^ Beggs AD, Jones A, El-Bahrawy M, El-Bahwary M, Abulafi M, Hodgson SV, Tomlinson IP (April 2013). "Whole-genome methylation analysis of benign and malignant colorectal tumours". The Journal of Pathology. 229 (5): 697–704. doi:10.1002/path.4132. PMC 3619233. PMID 23096130.
  6. ^ Novak K (December 2004). "Epigenetics changes in cancer cells". MedGenMed. 6 (4): 17. PMC 1480584. PMID 15775844.
  7. ^ Banno K, Kisu I, Yanokura M, Tsuji K, Masuda K, Ueki A, et al. (September 2012). "Epimutation and cancer: a new carcinogenic mechanism of Lynch syndrome (Review)". International Journal of Oncology. 41 (3): 793–797. doi:10.3892/ijo.2012.1528. PMC 3582986. PMID 22735547.