Figure 2. Epigenetic Potentiation Hypothesis. This schematic illustrates how epigenetic events (purple cells) can mimic genetic alterations (pink cells) or prime a cell for a genetic mutation. In this hypothesis the epigenetic events do not have to occur at each stage (similar to the hypothesis proposed by Dr. Ilyas et al. for oncogenesis¹), the hypothesis simply states the possibility of where these events can occur to aid in the process of cellular transformation. Normal cells (yellow cells) may be exposed to environmental factors that prime these cells by producing a pool of cells that have epigenetic modifications making the cells more susceptible to genetic mutation (step 1). The epigenetic modifications may act as an enabling mechanism which results in the cell acquiring one of the four characteristics of malignant cells listed in the figure (step 2). The numbers in yellow indicate the total number of characteristics the premalignant cells have acquired. The cells that have acquired the mutation begin to proliferate and struggle with the host to survive (step 3). As this process continues the cells must acquire more of the characteristics of malignant cells to survive. During the acquisition of the remaining characteristics epigenetics may act repeatedly as an enabling mechanism (step 5) by producing an epigenetic mimic of a genetic mutation (step 6). Epigenetic changes can alter the expression patterns of genes important in cellular pathways that are critical in the four characteristics of malignant cells, thus creating an epigenetic mimic of a genetic change. This epigenetic mimic may be solidified by an eventual genetic mutation (step 7). Eventually, a combination of epigenetic and genetic alterations accumulate in a cell resulting in a fully transformed state (step 8).