Role of the retinoblastoma gene in the initiation and progression of human cancer.

Retinoblastoma, although the most common malignant ocu- lar tumor in childhood, is still a rare human malignancy. Nev- ertheless, the characterization of the molecular steps involved in the development of this cancer and the isolation of the gene responsible for tumor initiation have provided fundamentally important knowledge regarding a class of human cancer genes which have been defined as tumor "suppressor" or "regulatory" genes by us (1) and "antioncogenes" by others (2). What- ever the terminology one wishes to use, the more important issue is that the retinoblastoma (Rb)' gene is representative of a class ofcancer genes in which the functional loss ofboth alleles is critical for tumor formation. In addition, recent evidence suggests that the loss of Rb gene function is not only causally related to the development of retinoblastoma and tumors that occur as second cancers in patients with the hereditary form of retinoblastoma, but also is a key factor in the initiation and/or progression of several of the most common human malignan- cies including those of lung, breast, and bladder.