Mechanisms Underlying Recurrent Genomic Amplification in Human Cancers

Focal copy-number increases (genomic amplification) pinpoint oncogenic driver genes and therapeutic targets in cancer genomes. With the advent of genomic technologies, recurrent genomic amplification has been mapped throughout the genome. Recurrent amplification could be solely due to positive selection for the tumor-promoting effects of amplified gene products. Alternatively, recurrence could result from the susceptibility of the loci to amplification. Distinguishing between these possibilities requires a full understanding of the amplification mechanisms. Two mechanisms, the formation of double minute (DM) chromosomes and breakage–fusion–bridge (BFB) cycles, have been repeatedly linked to genomic amplification, and the impact of both mechanisms has been confirmed in cancer genomics data. We review the details of these mechanisms and discuss the mechanisms underlying recurrence.