The work of Rogers et al. [62] and more recently Mathios et al. [60] on the epigenetic regulation of ZMIZ1 expression in human cancer, together with our finding that ZMIZ1 and ZMIZ2 are mutated with at least one non-silent alteration in at least one third of published human cuSCC genomes [1, 2] suggest that these genes may be an important initiating trunk mutation in human keratinocyte initiation and cuSCC progression. This evidence concerns the gene ZMIZ2 and cancer.