The first two studies identified deletion of CDKN2A in multiple human cancers in 1994 (Kamb et al., 1994; Nobori et al., 1994), and subsequent investigation uncovered that CDKN2A loss was restricted to a subpopulation of lung cancers with intact retinoblastoma (RB) (Otterson et al., 1994), which was further disclosed as reciprocal RB inactivation and CDKN2A expression in primary lung cancers and cell lines (Shapiro et al., 1995). Here, RB1 is linked to cancer.