Gene-amplification model of carcinogenesis.

A two-stage model of carcinogenesis is proposed based on recent evidence for the occurrence of proto-oncogenes in the vertebrate genome, evidence for gene amplification during carcinogenesis, and studies of the action of tumor promoters. The model is baed on the view that an increase in the level of gene product from such proto-oncogenes is sufficient to induce neoplastic transformation. It proposes that the initial step in carcinogenesis (initiation) is a mutation producing a tandem duplication of a proto-oncogene. Gene amplification can then occur by successive unequal sister chromatid crossing-over events in several cell cycles until sufficient gene product is produced to transform the cell.