RB1 and cancer: RB1 gene hypermethylation is a known contributor to the pathogenesis of many cancers, including hepatocellular carcinoma and RB.51 Through transcriptional silencing of tumor suppressor genes, methylation can effectively increase the rate of mutations, and both the mutations and DNA methylation are heritable.50 However, many experts feel that more definitive investigation into the role of methylation in OS tumorigenesis is necessary to reinforce its importance.