Loss of PTEN in is associated with increased risk of developing brain metastases in stage III melanoma patients and increases the rate of brain metastasis formation in a mouse model of BRAF-mutant melanoma.51,52 Although less common than PTEN loss, the PI3K/AKT pathway can be hyperactivated by mutation of E17K in AKT isoforms. This evidence concerns the gene PTEN and melanoma.