Despite this, multiple analyses have revealed significant CpG methylation of the p16INK4a promoter (CDKN2A gene) in OS.50,73 Aberrant methylation is also significant in tumor suppressor gene RASSF1A, which has been shown to inhibit accumulation of cyclin D, thereby promoting cell cycle arrest.50,74 Thus, the observed hypermethylation of CDKN2A and RASSF1A in OS samples leads us to infer that methylation-induced inactivation of these tumor suppressor genes may have a role in osteosarcomagenesis. This evidence concerns the gene RASSF1 and neoplasm.