Fig. 1

Reference epigenomes in cancer studies. Epigenetic studies use comparisons of normal and tumor samples to define disease-specific alterations. Even if those samples originate from the same patient (matching control, e.g., healthy tissue) and thereby exclude the detection of epigenetic variation based on environmental factors or aging, several other factors could potentially affect the analysis of disease-related epigenetic differences. The composition of cell types can differ between samples making the observed differences a mixture of cell-type-related and disease-specific divergences. The epigenome is also shaped during differentiation. Comparison of tumor and normal cells in different stages of differentiation would detect a mixture of differentiation- and disease-specific divergences. Therefore, factors affecting the normal epigenome have to be investigated and considered to define truly disease-specific epigenetic alterations