The role of alterations in the functioning of epigenetic machinery on thedevelopment and progression of clear cell renal cell carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is a very aggressive disease, thecause of which is not yet fully understood. Due to high resistance to treatment,resulting in high mortality, it is necessary to develop new, moreeffective targeted therapies based on the study of cancer mechanisms inccRCC. In ccRCC, abnormalities of metabolism and reprogramming ofgene expression as well as epigenetic changes in chromatin are observed.Mutations or epigenetic changes in several genes related to epigeneticmodifications and chromatin remodeling are responsible for the initiationof the carcinogenesis in ccRCC. These proteins form a system thatinfluences the availability of particular DNA sequences to other proteinsrelated to transcription, replication, recombination and repair. Mutationsin genes encoding subunits of the SWI/SNF chromatin remodeling complexor epigenetic silencing of their expression have been found in variouscancer types. The conducted studies have shown that ccRCC is characterizedby a disturbance in the expression of genes encoding tumorsuppressors a subunit of the SWI/SNF chromatin remodeling complex.Studies on the participation of the core INI1 subunit of the SWI/SNF complex in ccRCC have shown that the disturbance of the expressionlevel of these genes may be caused by mechanisms other than onlymutations. The data available in the literature and obtained in the project5/XVII/18 financed by the Polpharma Scientific Foundation clearly indicatethat epigenetic mechanisms play an important role in the control ofmachinery involved in the regulation of gene expression and they are asimportant as mutations.