CDKN2A and cancer: In most cases, OIS is characterized by the accumulation of p53 and/or p16INK4a following the activation of oncogenic pathways, whereas inactivation of p53 or p16INK4a following additional genetic lesions has been associated with an escape of senescence and malignant transformation of premalignant lesions in several cancers [93,100,101,102,103,104].