TUMOR-SUPPRESSOR GENES - NEW PERSPECTIVES FOR INVESTIGATION IN HUMAN CANCER

Tumor origin is viewed as comprising a series of specific genetic even ts in target cells and their clonal descendants. The development of mo lecular biology during the last decade has led to the recognition that these events fall into two distinct categories: the activation of pro tooncogenes and the inactivation of tumor suppressor genes. The latter are genes the inactivation of which is required for the malignant tra nsformation of a cell. Loss of tumor suppressor genes plays an importa nt role in the development of human tumors. Studies with somatic cell hybrids have shown that tumor suppression occurs in neoplastic cells a nd can be corrected by cell fusion with normal human chromosome. These experiments proved that tumorigenicity is a recessive phenotype contr olled by specific chromosomes. Certain tumor suppressor genes, e.g. p5 3 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. Th e detection of germline mutations in tumor suppressor genes should all ow the identification of subjects at high risk of developing cancer.