Gene amplifications and extrachromosomal circular DNAs: function and biogenesis

Gene amplification is an increase in the copy number of restricted chromosomal segments that contain gene(s) and frequently results in the over-expression of the corresponding gene(s). Amplification may be found in the form of extrachromosomal circular DNAs (eccDNAs) or as linear repetitive amplicon regions that are integrated into chromosomes, which may form cytogenetically observable homogeneously staining regions or may be scattered throughout the genome. eccDNAs are structurally circular and in terms of their function and content, they can be classified into various subtypes. They play pivotal roles in many physiological and pathological phenomena such as tumor pathogenesis, aging, maintenance of telomere length and ribosomal DNAs (rDNAs), and gain of resistance against chemotherapeutic agents. Amplification of oncogenes is consistently seen in various types of cancers and can be associated with prognostic factors. eccDNAs are known to be originated from chromosomes as a consequence of various cellular events such as repair processes of damaged DNA or DNA replication errors. In this review, we highlighted the role of gene amplification in cancer, the functional aspects of eccDNAs subtypes, the proposed biogenesis mechanisms, and their role in gene or segmental-DNA amplification.