TP53 and cancer: These consist of amplified segments of 12q13-15 that contain a number of cancer-related genes implicated in tumorigenesis.7 The most extensively studied of these are MDM2, an E3 ubiquitin protein ligase that acts as a key negative regulator of p53 and is amplified in nearly 100% of patients, and cyclin-dependent kinase 4 (CDK4), a key regulator of the G1/S cell cycle checkpoint that is coamplified with MDM2 in over 90% of patients8 (Fig 2C).