p53 is almost always inactivated in human cancers, either by mutation or indirectly through binding to viral proteins, or as a result of alterations in genes, whose products either activate, stabilize or carry signals from p53 including ARF, Wip1 and HDM2.36, 37, 43, 48 As neither U2OS nor HCT116 cells express ARF due to promoter methylation49, 50 (Supplementary Figure S4), LZAP regulation of p53 does not require ARF, as we previously reported. This evidence concerns the gene CDKN2A and cancer.