Periodic Reporting for period 2 - ONCOmetENHANCERS (Elucidating the Role of Enhancer Methylation Variation in Cancer and Developing Enhancer-based Markers and Targets for Precision Medicine)
Reporting period: 2018-10-01 to 2020-03-31
Cancer is a growing medical problem but its genetic and environmental bases are not clearly understood. In this regards, it belongs to a large group of common human diseases including metabolic, cardiovascular, autoimmune, psychiatric, and cancer illnesses which jointly affect hundreds of millions of people around the globe and their incidence and prevalence are rapidly growing. There is strong epidemiological evidence indicating complex genetic origins of these ailments along with a significant contribution from the environment, but the mechanisms underlying the vast majority of these diseases are still unknown. Our project aims at elucidating whether a particular research hypothesis, namely that variation in the epigenetic marks of gene regulatory components consist the missing mutational events that drive such complex diseases (Figure 1). If our hypothesis will be supported, it may provide a whole new understanding of the mechanism leading to the development of cancer and other diseases, and pave the way for the developing of improved tools for prediction, diagnosis, and treatment of the patients.
We suspect that a particular epigenetic mark called ‘DNA methylation’ tackles the normal communication between the environment and the genetic backgrounds of the patients, and by that cause the disease. The goal of our research is to determine if changes in the DNA methylation of particular components of the gene regulatory machinery, known as ‘cis-acting transcriptional enhancers’, may lead to malfunctioning of cancer driver genes, and by that form a significant part of the cellular mechanism underlie cancer. Therefore, we aim to map and explain the ways by which DNA methylation affect the regulatory circuits of key genes that drive cancer risk, initiation and development.