For example, mice carrying heterozygous deletions of SAC genes, such as MAD1, MAD2, and BUB1B, exhibit increased CIN and develop spontaneous tumors.106–108 Similar evidence comes from human patients with mosaic variegated aneuploidy syndrome (MVA), which is characterized by increased CIN and a predisposition to childhood cancer.109,110,262,263 These results suggest that tumor cells may exploit CIN to harness the potential of clonal evolution for optimal adaptation. This evidence concerns the gene BUB1B and cervical squamous intraepithelial neoplasia.