Tumor-Suppressor Genes As their name implies, tumor-suppressor genes are normally protective, acting to prevent the unregulated growth that is characteristic of a cancer cell. They can also prevent the cancer-predisposing effect of an activated oncogene. If one of these genes is absent or its protein product is unable to work properly, the cancer-producing action of an undetected oncogene may not be completely suppressed and a tumor may develop.
Many tumor-suppressor genes have been identified recently. Some are referred to by their protein size—p53, for example—while others are named for the cancer in which they were first discovered, as in WT (Wilms' tumor) and RB (retinoblastoma).
Tumor-suppressor genes are most commonly discovered in inherited cancers, since abnormal forms of these genes are passed to offspring by either egg or sperm. But they also play important roles in non-inherited cancers. Almost all cancers show a defect in one or more tumor- suppressor genes. A typical colon cancer, for example, may have at least four inactivated tumor-suppressor genes (p53, DCC, APC and MCC).
The RB gene was the first tumor-suppressor gene to be discovered and characterized, and retinoblastoma remains the model of a cancer caused by the loss of a tumor-suppressor gene product. Retinoblastoma is a rare and often fatal eye cancer occurring in children. It may be inherited or arise spontaneously.
• In the inherited form, one RB gene derived from one parent is non-functional. Sometime during childhood, the
normal RB gene from the other parent becomes lost or mutated, predisposing cells in the retina to form a
