**5. Conclusion**

Epigenome in a typical eukaryotic cell is packaged as an entity containing nucleoproteins-DNA and histones. This epigenome is compartmentalized into euchromatin and heterochromatin and contain various marks which are transmitted from one cell generation to another [127]. Covalent DNA and histone modifications are the carriers of epigenetic inheritance which are required for the maintenance of a stable epigenome [128]. Any disturbance in the propagation and maintenance of a stable epigenome is associated with diseases like transformation and cancer. The process of cellular transformation is associated with changes in the epigenetic landscape of DNA methylation and histone post-translational modifications. In recent past, genome wide studies have identified various genes related to diseases like cancer and neurodegeneration [4]. Many of these genes have been observed to code for key epigenetic enzymes like HDACs, which raises the possibility of their involvement in far reaching pathological problems. In recent years, non-coding RNA has also been increasingly investigated in relation to carcinogenesis and various types of non-coding RNAs have been associated with different forms of cancer [129, 130].

A stable epigenome also requires proper chromatin conformation. It has been observed that upon transformation, the 3D organization and nuclear topology also undergoes certain changes. These topological changes can be both cause and consequence of alterations in histone and DNA modifications. Topological changes in chromatin structure are associated with increased expression of repetitive DNA elements, which leads to hyper-recombination and gross genomic instability which can further lead a cell on the path of transformation.

Studies performed on chromatin structure and covalent modifications have paved way for better understanding as well as therapeutic intervention of various forms of cancer. Epigenetic approach of therapeutic intervention in cancer is definitely a better approach for cancer treatment since it aims at reversal of inheritable changes without changing the DNA or without affecting normal physiological processes. Also, tumor forms have recently been discovered with anatomical restrictions which contain mutations in histone variant genes. For example, H3.3, a variant of histone H3, contains a point mutation at residue 34 in which glycine changes to valine or arginine (H3.3G34V or H3.3G34R). These tumors are found almost exclusively in the cerebral hemispheres [131, 132]. Tumors with point mutations in histone variant H3.1 (H3.1K27M) are restricted to pons of brainstem while as H3.3K27M tumors are found along the midline of the brain [133]. This "anatomical restriction" in tumor types and the corresponding mutations in histone variants are indicative of an exciting new dimension of the role of epigenetics in tumor biology [134, 135]. This also provides cues about the role of epigenetics in defining tumor micro-environment. Alternatively, many more tumor types can be screened for mutations in genes coding

### **Figure 4.**

*Schematic depicting two major pillars of epigenetic mechanisms that is, DNA methylation and histone modifications, their importance in maintaining normal cellular morphology and function and their mis-regulation leading to cancer.*

for epigenetic factors to have better insights into the role of epigenetics in tumor progression. These findings also encourage the possibility of exploration of epigenetic therapy in resetting the balance in tumor micro-environment for therapeutic targeting. However, the field of epigenetic studies and epigenetic cancer therapy is still in its infancy and intense investigations are required for further exploration of the possibility of epigenetic targeting and treatment of cancer (**Figure 4**).

*Evolution of Epigenome as the Blueprint for Carcinogenesis DOI: http://dx.doi.org/10.5772/intechopen.97379*
