Mutations frequently occurred in the components of PI3K/AKT signaling pathway, such as the well-established loss-of-function mutations of PTEN39 and von Hippel-Lindau tumor suppressor (VHL)40 or gain-of-function mutations of PIK3CA41, KRAS42 or AKT43, all contribute to AKT kinase activity and cancer cell malignancies. This evidence concerns the gene VHL and cancer.