Epigenetic Regulatory Enzymes: mutation Prevalence and Coexistence in Cancers.

Epigenetic regulation is an important layer of transcriptional control with the particularity to affect the broad spectrum of genome. Over the years, largely due to the substantial number of recurrent mutations, there have been hundreds of novel driver genes characterized in various cancers. Additionally, the relative contribution of two dysregulated epigenomic entities (DNA methylation and histone modifications) that gradually drive the cancer phenotype remains in the research focus. However, a complex scenario arises when the disease phenotype does not harbor any relevant mutation or an abnormal transcription level. Although the cancer landscape involves the contribution of multiple genetic and non-genetic factors, herein, we discuss specifically the mutation spectrum of epigenetically-related enzymes in cancer. In addition, we address the coexistence of these two epigenetic entities in malignant human diseases, especially cancer. We suggest that the study of epigenetically-related somatic mutations in the early cellular differentiation stage of embryonic development might help to understand their later-staged footprints in the cancer genome. Furthermore, understanding the co-occurrence and/or inverse association of different disease types and redefining the general definition of "healthy" controls could provide insights into the genome reorganization.