CDKN2A and lung cancer: DNMT3a and DNMT3b are methyltransferases that establish novel methylation patterns by targeting normally unmethylated CpG sites.[35] DNMT1 expression is increased early in lung cancer and is directly involved in the silencing of multiple genes involved in lung cancer pathogenesis, such as RASSF1A and CDKN2a.[36,37] DNMT1 and DNMT3b cooperate to establish aberrant DNA methylation and chromatin complexes to inhibit TSGs.[38] DNMT3b overexpression accelerates carcinogen-induced cell line transformation, is frequently observed in lung cancer, and is associated with poor prognosis.[39,40]