Amplification is the selective increase of DNA copy number either intracellularly, as a local genomic change, or experimentally, by polymerase chain reaction (PCR). Increase of the level of mRNA or protein alone should not be referred to as amplification.
Scheduled amplification as part of a developmental gene expression program, e.g., chorion genes in ovaries of the fruit fly Drosophila melanogaster or actin genes during myogenesis in the chicken.
Unscheduled amplification during acquisition of cellular drug resistance. For example, amplification of the gene encoding dihydrofolate reductase (DHFR) can result in up to 1,000 gene copies per cell with the consequence of cellular resistance against the chemotherapy drug methotrexate.
Unscheduled amplification of cellular genes involved in growth control (oncogenes) during tumor progression. Amplification of oncogenes can result in up to several hundred gene copies and enhanced gene expression. Usually large DNA stretches (from 100 Kb up to several Mb) are amplified, and therefore syntenic genes in addition to the particular oncogene can be co-amplified due to their close linkage to the oncogene. Alternatively, different non-syntenic oncogenes can amplify independently in the same cell. The prototypic human cancer with oncogene amplification is neuroblastoma. Here, the amplified gene, MYCN, is a biomarker for patient management.
Resistance against cytostatic drugs poses a big problem in cancer therapy. Amplified oncogenes contribute to tumor progression, many different oncogenes have been found amplified (e.g., RAS , MYC , MYCN , MYCL , HER-2 ( HER-2/neu ), ABL in some tumor types the oncogene status provides information about patient prognosis: Amplified MYCN indicates poor prognosis for stage 1–3 neuroblastoma; and amplified HER-2 indicates unfavorable outcome in a subgroup of breast cancer.