Amplification of oncogenes in human cancer cells.

Gene amplification refers to a genomic change that results in an increased dosage of the gene(s) affected. Amplification represents one of the major molecular pathways through which the oncogenic potential of proto-oncogenes is activated during tumorigenesis. The architecture of amplified genomic structures is simple in some tumor types, involving in the vast majority of cases only one gene, such as MYCN in neuroblastomas. On the other hand, it can be complex and discontinuous, involving several syntenic co-amplified genes, such as in the 11q13 amplification in breast cancer, although in many of these cases there may be a single target gene. The presence of different nonsyntenic amplified genes raises the possibility that cells of certain tumors are susceptible to independent amplification events. In general, the amplified genes do not undergo additional damage by mutations. The data indicate that it is the enhanced level of a wild-type protein that contributes to tumorigenesis.