Among all the CKIs, p16/INK4A is the founding member and was the first classified as a major tumor suppressor gene (only preceded by p53 for many human malignancies) because the mutations in the INK4A/ARF locus, and loss of heterozygosity of the chromosomal region encoding this gene, have been reported in a wide range of cancers including melanomas, leukemias, gliomas, lung, breast and bladder cancers [36,41]. Here, CDKN2A is linked to cancer.