Succinate: a new epigenetic hacker

Abstract

Epigenetic reprogramming is a feature of many human cancers. In this issue of Cancer Cell, Letouzé and colleagues describe DNA hypermethylation in paragangliomas harboring mutations in succinate dehydrogenase genes. These tumors accumulate succinate, which inhibits 2-oxoglutarate-dependent histone and DNA demethylase enzymes, resulting in epigenetic silencing that affects neuroendocrine differentiation.