FIGURE 24-12 The development and metastasis of human colorectal cancer and its genetic basis. A mutation in the APC tumor-suppressor gene in a single epithelial cell causes the cell to divide (although surrounding epithelial cells do not), forming a mass of localized benign tumor cells, called a polyp. Subsequent mutations lead to expression of a constitutively active Ras protein and loss of the tumor-suppressor gene p53. These mutations, together with additional genetic changes yet to be identified, generate a malignant cell. The cell continues to divide, and its progeny invade the basement membrane that surrounds the tissue, but do not penetrate the basement membrane of capillaries (bottom left). Some tumor cells spread into blood vessels that will distribute them to other sites in the body (bottom right). Additional mutations permit the tumor cells to exit from the blood vessels and proliferate at distant sites. See B. Vogelstein and K. Kinzler, 1993, Trends Genet. 9:138–141.