EPAS1 and neoplasm: Inactivating mutations in the von Hippel–Lindau (VHL) tumor-suppressor gene account for the majority of sporadic clear cell cancers.1 Loss of VHL function leads to accumulation of the α-subunits of hypoxia-inducible factor (HIF) transcription factors (HIF-1α and HIF-2α) that dimerize with HIF-1β and transactivate HIF target genes such as vascular endothelial growth factor (VEGF).