The renewed interest in cancer cell metabolism has sparked novel insight into how the enzymes constituting the classic metabolic pathways impact carcinogenesis. In this issue of the GeneTex Epigenetics Newsletter, we would like to introduce several of our antibody reagents against certain cytoplasmic and mitochondrial enzymes whose mutational inactivation leads to accumulation of oncogenic metabolites. These metabolites inhibit key histone (e.g., the KDM5C and KDM6A H3 demethylases) and DNA (i.e., TET2) epigenetic modifiers and are likely to play central roles in the genesis of many cancers.
Kaelin and McKnight (Cell 153, 2013) present a comprehensive overview of how perturbations in the cell's metabolic state can potentially alter its epigenome, precipitating cancer and other diseases. Relevant to the theme of this newsletter is their discussion of how mutations in components of the mitochondrial succinate dehydrogenase (SDH) complex, fumarate hydratase (FH), and isocitrate dehydrogenases (IDH1/2) have been linked to a number of malignancies. As noted above, the underlying mechanism appears to involve increased levels of specific "oncometabolites" that inhibit crucial DNA- and histone-modifying factors.
The Keystone Symposia meeting on Cancer Epigenetics will be held in Santa Fe, New Mexico, USA during February 4-9, 2014. The goal of the meeting is to bring together scientists involved in basic, translational, or clinical research that focuses on understanding epigenetic states in normal and malignant cells. This will include work on epigenome mapping as well as genetic and biochemical studies of the key molecular players that establish and maintain these states. There will be joint keynote and plenary sessions with the concurrent meeting on Transcriptional Regulation. For deadlines and other information, please see the meeting website.