Oncometabolite dysregulation and cancer progression are linked to epigenetic changes in cancer cells. Several mechanisms have been linked to -2-hydroxyglutarate, succinate, and fumarate with the inhibition of α-KG–dependent dioxygenases, this causes epigenetic changes that affect the expression of genes involved in cell differentiation and the development of malignant characteristics. The group of Timothy A. Chan described a mechanism by which abnormal accumulation of the oncometabolite -2-hydroxyglutarate in brain tumor samples increased DNA methylation, a process that has been shown to play a key role in oncogenesis. On the other hand, in paraganglioma cells, succinate and fumarate were found to methylate histones, effectively silencing the genes PNMT and KRT19, which are involved in neuroendocrine differentiation and epithelial-mesenchymal transition, respectively.