Alteration of the genomes of tumor cells

The transfer of DNA from tumor cells into normal cells has made possible the definition of oncogenes in the DNA of the donor tumor cells. Some of these oncogenes have been isolated by molecular cloning and found to derive from closely related normal cellular sequences. These normal antecedents are termed proto-oncogenes. Analysis of molecular clones of the proto-oncogene and its transforming allele indicate that the two genes are very similar. In one case the alteration of a single nucleotide in the normal gene resulted in the creation of an active oncogene. This point mutation affected a sequence encoding the 21,000 dalton protein, resulting in a glycine at its residue 12 being replaced by a valine. This altered protein mediates the resulting transformation of the cell. Such altered proteins are found in a number of lung and colon carcinomas. Although these oncogenes represent important determinants of the carcinogenic process, other genetic alterations appear to be necessary in order to achieve full conversion of a normal cell into a tumor cell.