CDKN2A and neoplasm: These observations are consistent with the finding that inactivation of p53 and p16INK4A in oral premalignant and malignant cells results in only minor chromosomal alterations but, following telomerase deregulation and cellular immortalization, extensive SCNA and LOH are observed [50,75], suggesting that the emergence of cells from crisis [27] is a key and rate-limiting step in tumour progression.