Introduction
Development of cancer has long been considered to be the consequence of a
wide variety of genetic alterations such as chromosomal translocations, point
mutations and deletions that alter proliferation and survival by activating
oncogenes or by inactivating tumor-suppressor genes. Whereas these genetic
changes constitute the basis of transformation, recent discoveries suggest
additional levels of gene regulation that may play a key role in tumor
heterogeneity and progression, which are generally referred to as epigenetic.
The term “epigenetic” encompasses the sum of heritable modifications that do
not involve changes to the underlying DNA sequence.
Different mechanisms can initiate and sustain epigenetic changes and a
complex interplay of these different mechanisms is beginning to be elucidated.
Epigenetic modifications include: DNA methylation, which generates 5-
methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), post-translational
histone tail modifications, including methylation, acetylation, phosphorylation
and ubiquitylation, energy-dependent nucleosomal remodeling, and long
noncoding RNA regulation of local chromatin structure and chromosome
organization.