FH and neoplasm: In summary, our investigations have revealed that despite the striking upregulation of the HIF transcriptional cascade in FH-associated neoplasia, these pathways do not appear to contribute to hyperplastic renal cyst formation, at least in a mouse model that recapitulates many features of the human disease; rather, our findings have raised the possibility of an alternative oncogenic action of fumarate through the activation of antioxidant response pathways by succination of KEAP1, and possibly other proteins with tumor suppressor functions.