In cell lines we could establish that HIF-2 was active at a subphysiological level of oxygenation (5% oxygen) and transcribing known hypoxia-driven genes such as VEGF. Importantly, presence of tumor cells with strong immunohistochemical staining for HIF-2α correlates to high clinical neuroblastoma stage and unfavorable outcome (17). This evidence concerns the gene VEGFA and neuroblastoma.