Tumor suppressor genes. New perspectives for clinical investigations in cancer

Tumor origin is viewed as comprising a series of specific genetic events in target cells and their clonal descendants. The development of molecular biology during the last decade has led to the recognition that these events fall into two distinct categories: the activation of protooncogenes and the inactivation of tumor suppressor genes. The latter are genes the inactivation of which is required for the malignant transformation of a cell. Loss of tumor suppressor genes plays an important role in the development of human tumors. Studies with somatic cell hybrids have shown that tumor suppression occurs in neoplastic cells and can be corrected by cell fusion with normal human chromosome. These experiments proved that tumorigenicity is a recessive phenotype controlled by specific chromosomes. Certain tumor suppressor genes, e.g. p53 and RB1, may be involved in a variety of malignancies whereas others, e.g. the DCC gene, may be restricted to a single type of cancer. The detection of germli...