The gene responsible for the formation of both retinoblastoma and osteosarcoma recently has been isolated. This represents the first human recessive cancer gene ever cloned. Structural deletions within one or both retinoblastoma gene alleles were commonly noted in the retinoblastomas and an osteosarcoma. Whether or not changes were observed at the DNA level there was either no expression or an abnormal expression of the gene in the tumor. The fact that we could detect changes in the fibroblasts of some patients with the hereditary form of retinoblastoma also indicates that the gene can be used for diagnostic purposes.
Cancer 621691-1694, 1988.
HERE ARE MANY human cancers for which a hered-T itary predisposition plays a key role in tumor development. In addition there are subsets of individuals for almost all cancers for which heredity is fundamentally important in the etiology of their cancer. Studies in molecular biology are now providing key data to understand the events responsible for tumorigenesis. In fact, the gene has been isolated that is responsible for the development of at least two malignancies, namely retinoblastoma (Rb) and osteosar~oma.'-~ Retinoblastoma is the most common intraocular tumor in childhood and osteosarcoma is a bone tumor which affects both children and adults. In this article, after discussing the genetics of retinoblastoma development, we shall document some of the molecular changes responsible for the formation of retinoblastoma and osteosarcoma. We shall also explain how the cloned Rb gene can be used to identify individuals who have inherited the gene.