Rb seemed to be important in both cell cycle exit as well as formation of SAHF: compromise of the Rb pathway through loss of p18Ink4c (the major known function of which is inhibition of Cdk4/6 to indirectly activate Rb [38-40]) led to a delay in initial cell cycle exit, and eventually to complete penetrance of tumor progression within the senescent-like lesion. This evidence concerns the gene RB1 and neoplasm.