We are investigating the structural organization and functional significance in tumor cells of chromosomal anomalies termed (1) homogeneously staining regions (HSRs) and (2) double-minute chromosomes (DMs). We have obtained evidence that DMs and HSRs present in related lines of Y1 mouse adrenocortical tumor cells are similar in molecular composition and result from a process of gene amplification. An analysis of DMs in a transformed derivative of 3T3 mouse cells revealed that DMs in these cells also result from gene amplification, but the amplified sequences are different from those in the Y1 cells. We have demonstrated that cellular sequences related to the transforming gene (oncogene) of the Kirsten sarcoma virus (Ki-ras) are amplified 30- to 60-fold in the Y1 cells, and the amplified sequences are present on DMs and HSRs. Further, the level of the cellular Ki-ras-specific mRNA and of the protein p21 coded for by this gene are elevated in these cells. Studies in progress should provide information concerning: (1) the organization of the amplified DNA; (2) the number of genes amplified; and (3) the mechanisms by which the amplification and enhanced expression of cellular oncogenes might contribute to the initiation and/or maintenance of neoplastic transformation of some cells. (I)
