Several reasons led us to build this specific model: (1) human orthologs of these genes are co-mutated in subsets of human cancer samples [47,48]; (2) alterations in the canonical pathways to which these genes are attributed, i.e. RB1, cell cycle; PTEN, PI3K/Akt signaling, and RAS, RTK-RAS signaling, co-occur in multiple cancer types [43]; (3) mutations in these three genes are among the most significant drivers of metastasis [1]; and (4) functional interaction, in terms of tumorigenesis, between orthologs of these genes has previously been demonstrated in mouse models. This evidence concerns the gene PTEN and cancer.