TP53 and neoplasm: The Ink4a/Arf genetic locus encodes two tumor suppressor genes, namely p16Ink4a and p19Arf, acting on separate pathways: p16Ink4a is an inhibitor of the CDK46/cyclin D kinases and, therefore, functions as a positive regulator of the Retinoblastoma family of proteins; p19Arf is an inhibitor of the ubiquitin ligase MDM2, thereby, stabilizing p53 (Gil & Peters, 2006).