MDM2 overexpression, an upstream negative regulator of p53, and downregulation of PERP, a downstream effector of p53, have been demonstrated in many UM patients and are associated with worse outcome.96-100 Studies have also shown that over half of UM tumors have decreased PTEN immunostaining and its loss is correlated with decreased survival.67-69 Nevertheless, whether genetic knockout of these tumor suppressors recapitulate the dysregulation of these pathways in human UM remains an open question. The gene discussed is PTEN; the disease is neoplasm.