## Epigenetic modifications play a role in the development of human diseases

Many studies suggest that changes in the epigenetic profile may disrupt biosynthetic pathways in cells and play a key role in the development of some human diseases. Currently, there are already known examples of certain diseases whose development or progression depends to some extent on epigenetic changes. The mechanism of carcinogenesis involves alteration at the genetic level, primarily through the activation of oncogenes (genes whose mutations lead to the development of cancer) or the inactivation of anti-cancer tumour suppressor genes as a result of various mutations (explained in detail in Chapter 9 – When cells go crazy). However, recent research shows that extensive epigenetic modifications also occur in tumour cells that can alter the expression of genes critical for cancer development, namely global hypomethylation (insufficient methylation) of DNA and hypermethylation (excessive methylation) of tumour suppressor genes. An altered state of the epigenome contributing to carcinogenesis has been observed in many types of oncological diseases. In acute myeloid leukaemia, alterations in the epigenome have been found to be caused in part by mutations in genes encoding enzymes responsible for DNA methylation/demethylation. An example is lung cancer, where DNA hypermethylation has been shown to occur in early stages of the disease as well as in advanced stages, with up to 3% of all functional genes containing CpG-rich regions being deactivated by methylation. Epigenetic alterations have also been studied in childhood gliomas, gastric cancer, and skin melanoma. Intensive research is therefore being conducted in the field of cancer therapy to use new knowledge in diagnosis and, at the same time, to find suitable therapeutic agents that can correct defective epigenetic marks in tumour cells. Azacytidine is a substance that causes the removal of methyl groups from DNA (demethylation). The drug is one of the therapies also used in clinical practice in the treatment of patients with myelodysplastic syndrome, a hematopoietic disorder often referred to as preleukemia.

In addition to cancer, however, there are other diseases in the development of which the epigenome plays an important role. One group of such diseases is autoimmune diseases, including systemic lupus erythematosus, which affects the skin, joints, kidneys or nervous system, rheumatoid arthritis (inflammatory joint disease) or multiple sclerosis, which affects the brain. The link is also observed in endocrine diseases such as type II diabetes, respiratory diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis), but also skin diseases (psoriasis or systemic sclerosis). The role of the epigenome has already been demonstrated in diseases of the cardiovascular system, manifested by atherosclerosis, hypertension, and heart failure. Digestive tract diseases associated with epigenome changes include inflammatory bowel diseases (Crohn's disease, ulcerative colitis) and liver cirrhosis.