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Extrachromosomal DNA amplifications in cancer

Item Type:Review
Title:Extrachromosomal DNA amplifications in cancer
Creators Name:Yi, E. and Chamorro González, R. and Henssen, A.G. and Verhaak, R.G.W.
Abstract:Extrachromosomal DNA (ecDNA) amplification is an important driver alteration in cancer. It has been observed in most cancer types and is associated with worse patient outcome. The functional impact of ecDNA has been linked to its unique properties, such as its circular structure that is associated with altered chromatinization and epigenetic regulatory landscape, as well as its ability to randomly segregate during cell division, which fuels intercellular copy number heterogeneity. Recent investigations suggest that ecDNA is structurally more complex than previously anticipated and that it localizes to specialized nuclear bodies (hubs) and can act in trans as an enhancer for genes on other ecDNAs or chromosomes. In this Review, we synthesize what is currently known about how ecDNA is generated and how its genetic and epigenetic architecture affects proto-oncogene deregulation in cancer. We discuss how recently identified ecDNA functions may impact oncogenesis but also serve as new therapeutic vulnerabilities in cancer.
Keywords:Cancer Genetics, Cancer Genomics, Genomic Instability
Source:Nature Reviews Genetics
ISSN:1471-0056
Publisher:Nature Publishing Group
Date:11 August 2022
Official Publication:https://doi.org/10.1038/s41576-022-00521-5
PubMed:View item in PubMed

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