The Importance of Aberrant DNA Methylation in Cancer

Cancer has long been considered primarily a genetic disease, caused by different mutations throughout the genome. In 1983., Feinberg and Vogelstein discovered that the level of DNA methylation significantly varies between primary human malignant tumors and their normal counterparts (Feinberg & Vogelstein, 1983). Before this publication, there had been a paper describing changes in DNA methylation in cancer cell cultures, including the influence of N-methyl-N-nitrosourea on the level of DNA methylation in Raji cells (Boehm & Drahovsky, 1981). Currently, we are presented with much experimental data showing multilevel changes in cancer cells. In this context, two major areas of epigenomic research DNA methylation and histone modifications appear most promising in understanding the multistep nature of carcinogenesis. Additionally, they seem to have the potential for being cancer biomarkers, useful in early detection, in predicting the biological behavior of tumors and for therapy monitoring, as recently reviewed (Rodriguez-Paredes & Esteller, 2011; Baylin & Jones, 2011). Finally, epigenetic changes are well-recognized targets for cancer therapy, alone, or in combination with various cytostatics (Ren et al, 2011). Epigenetic changes are also of the greatest importance in chemoprevention, as there is increasing data relating to possibly reversing epigenetic changes in the earliest phase of carcinogenesis, when genetic changes have yet to develop (reviewed, Huang et al., 2011). It is not easy to understand the particular rules applicable to epigenomic processes. If one specific epigenetic change, relating to a specific gene/its promoter, exists in a majority of tumors of a specific type, it does not necessarily mean that the same change exists in another type of tumor. This is consequential, and represents one reason for obvious differences in responses to epigenomic therapy. Recently, we wrote a review article on some aspects of epigenomic changes in which we used the term „epigenetic networking“. If we imagine each of our living cells as an orchestra performing the symphony of life, then each player (a gene) of the orchestra needs to play in concert with 30,000 other players. The communication that produces the network of our epi-genome is established at many levels: transcriptionally, post-transcriptionally, through protein translation, at the level of post-translational protein modifications, through their orchestrated interactions and, finally, their interaction with the DNA that can be modified in order to accept or reject the protein partner. This is the way of