For example, glutathione peroxidase 4 (Gpx4) deficiency in myeloid cells induces tumorigenesis in various tissues and malignant progression of colorectal tumors through reactive oxygen species–mediated epithelial and/or tumor mutagenesis, including mutations in the driver genes: Apc, kras, and Tp53 (6), indicating stromal cell–dependent mechanisms underlying the epithelial and/or tumor cell–intrinsic mutations that cause tumor development and malignant progression. This evidence concerns the gene APC and neoplasm.