SMAD4 and cervical squamous intraepithelial neoplasia: Previously, Martins et al. reported that high MYC is an early event selected in many tumors with CIN, thereby providing a selective growth advantage to the tumor cells.291–293 Incorrect repair can also lead to a complete loss of gene function, such as the loss of key tumor suppressor gene mothers against decapentaplegic homolog 4 (SMAD4),294 as well as generation of novel oncogenic proteins by chromosome fusion.