DNA methylation and carcinogenesis

The hypothesis of the exclusively genetic origin of cancer ("cancer is a di sease of genes, a tumor without any damage to the genome does not exist") d ominated in the oncology until recently. A considerable amount of data conf irming this hypothesis was accumulated during the last quarter of the last century. It was demonstrated that the accumulation of damage of specific ge nes lies at the origin of a tumor and its following progression. The damage gives rise to structural changes in the respective proteins and, consequen tly, to inappropriate mitogenic stimulation of cells (activation of oncogen es) or to the inactivation of tumor suppressor genes that inhibit cell divi sion, or to the combination of both (in most cases). According to an altern ative (epigenetic) hypothesis that was extremely unpopular until recently, a tumor is caused not by a gene damage, but by an inappropriate function of genes ("cancer is a disease of gene regulation and differentiation"). Howe ver, recent studies led to the convergence of these hypotheses that initial ly seemed to be contradictory. It was established that both factors-genetic and epigenetic-lie at the origin of carcinogenesis. The relative contribut ion of each varies significantly in different human tumors. Suppressor gene s and genes of repair are inactivated in tumors due to their damage or meth ylation of their promoters (in the latter case an "epimutation", an epigene tic equivalent of a mutation, occurs, producing the same functional consequ ences). It is becoming evident that not only the mutagens, but various fact ors influencing cell metabolism, notably methylation, should be considered as carcinogens.