Cancer genes.

Cancer is a genetic disease; tumor cells differ from their normal progenitors by genetic alterations that affect growth-regulatory genes. There exist 2 classes of such cancer genes: the oncogenes, which function as positive growth regulators, and the tumor suppressor genes, which function as negative growth regulators. Oncogenes are widely conserved among diverse forms of life and are active in transmitting growth signals from the cell periphery to the cell nucleus. These signaling functions can be disturbed by many types of genetic change; the result of an altered growth signal is often cancer. Tumor suppressor genes have an attenuating effect on cell growth that is lost as a result of inactivating mutations or deletion of the gene; in DNA virus-transformed cells, it is abrogated by neutralization of the tumor suppressor protein through a viral gene product. Tumor suppressor genes were first recognized in inherited cancers; defects in a tumor suppressor transmitted through the germ line can lead to increased tumor incidence in the offspring. Tumor suppressors also play important roles in nonheritable cancer, however; many tumors in humans show defects in tumor suppressor genes. Most cancers harbor multiple genetic changes in oncogenes as well as tumor suppressor genes. Oncogenes induce aberrant growth through a gain in function; tumor suppressor genes contribute to oncogenesis through a loss of function. Both types of mutation work together to produce cancer; the changes are not constant but increase in number as the tumor develops from benign to more and more malignant. Cancer results from the accumulation of genetic changes. Oncogenes and tumor suppressor genes provide important insights into the regulation of cell growth. This knowledge can now be used to develop gene-specific therapies for cancer.