Connecting the dots: Epigenetic regulation of extrachromosomal and inherited DNA amplifications

DNA amplification has intrigued scientists for decades. Since its discovery, significant progress has been made in understanding the mechanisms promoting DNA amplification and their associated function(s). While DNA copy gains were once thought to be regulated purely by stochastic processes, recent findings have revealed the important role of epigenetic modifications in driving these amplifications and their integration into the genome. Furthermore, advances in genomic technology have enabled detailed characterization of these genomic events in terms of size, structure, formation, and regulation. This review highlights how our understanding of DNA amplifications has evolved over time, tracing its trajectory from initial discovery to the contemporary landscape. We describe how recent discoveries have started to uncover how these genomic events occur by controlled biological processes rather than stochastic mechanisms, presenting opportunities for therapeutic modulation.