HIF-2α accumulation, rather than HIF-1α, is a major phenomenon in VHL tumors and it results in the overexpression of hypoxia-induced angiogenic genes, such as vascular endothelial growth factor (VEGF), erythropoietin (EPO) and EPO-receptor, cyclin D1 (CCND1), and other genes involved in extracellular matrix reorganization that facilitate tumor development (45, 84). This evidence concerns the gene CCND1 and von Hippel-Lindau disease.