Chromosome abnormalities in human cancers are of at least two types: those specific to a particular cancer, such as the 13q deletion in retinoblastoma, and those non-random changes, such as the homogeneously staining region (HSR), which not restricted to any one malignancy. This suggests that gene changes in cancer may also be of two types: specific changes which are involved in tumorigenesis and other changes which play a role in tumor progression. We propose to begin a study of the roles played by individual genes in the development of a particular cancer, retinoblastoma, by focusing on the gene(s) which have been amplified in the HSR in a retinoblastoma cell line. We will use chromosome isolation and molecular genetic techniques to prepare recombinant probes (containing sequences unique to the amplified gene(s) to study gene amplification in this cancer. The experience gained in this pilot project should make it possible for us to propose a similar approach to the isolation and characterization of the gene(s) involved in tumorigenesis in retinoblastoma.