The retinoblastoma gene and gene product

Retinoblastoma, an uncommon childhood cancer of the eye, sometimes occurs in families but is often sporadic. Cytological analysis suggested that the retinoblastoma gene resided on chromosome 13 band q14. Subsequent isolation of the RB gene from this locus allowed a more detailed analysis, showing that both copies of RB are mutated or lost in retinoblastoma, a finding that has been extended to a surprising number of other malignancies. In familial retinoblastoma, one copy of RB is mutant in the conceptus, consistent with the familial predisposition to the disease and indicating that a single wild type copy is sufficient for normal development. These studies provided the first good evidence that loss of a gene function correlated with tumorigenesis and led to the concept of "tumour suppressor genes", which have an important negative influence on the regulation of cell growth. Examinations of the biological properties of the gene product are consistent with this proposed role in cell proliferation. Further insight into the potential molecular mechanisms concerned has come from observations showing an association of some viral oncoproteins with the RB gene product. Thus, there is strong evidence that the RB protein has a key role in the integrated network of signals that control the cell cycle.