Notably, this experimental system relies on single, defined genetic mutations for tumor initiation and progression, and thus allows for the dissection of complex cancer-related DNA methylation changes (Figure 1C): (1) Tumor-related changes can be identified through comparisons between normal lung and Dnmt3awt tumors; (2) Dnmt3a-related changes can be identified through comparisons between Dnmt3awt and Dnmt3aKO tumors; (3) methylation patterns of Dnmt3a mutant tumors can be modelled by identifying methylation differences between normal lung and Dnmt3aKO tumors (Figure 1C). This evidence concerns the gene DNMT3A and cancer.