Inactivating mutations in TCA cycle enzymes fumarate hydratase (FH) and succinate dehydrogenase (SDH) are driver mutations in a subset of human cancers and they mediate epigenetic reprogramming.83 SDH mutations are present in gastrointestinal stromal tumors (GISTs), renal cell carcinoma, paraganglioma and pheochromocytoma. The gene discussed is SDHB; the disease is hereditary clear cell renal cell carcinoma.