The genomic and spatial mobility of extrachromosomal DNA and its implications for cancer therapy

Item Type:	Article
Title:	The genomic and spatial mobility of extrachromosomal DNA and its implications for cancer therapy
Creators Name:	van Leen, E. and Brückner, L. and Henssen, A.G.
Abstract:	Extrachromosomal DNA (ecDNA) amplification has been observed in at least 30 different cancer types and is associated with worse patient outcomes. This has been linked to increased oncogene dosage because both oncogenes and associated enhancers can occupy ecDNA. New data challenge the view that only oncogene dosage is affected by ecDNA, and raises the possibility that ecDNA could disrupt genome-wide gene expression. Recent investigations suggest that ecDNA localizes to specialized nuclear bodies (hubs) in which they can act in trans as ectopic enhancers for genes on other ecDNA or chromosomes. Moreover, ecDNA can reintegrate into the genome, possibly further disrupting the gene regulatory landscape in tumor cells. In this Perspective, we discuss the emerging properties of ecDNA and highlight promising avenues to exploit this new knowledge for the development of ecDNA-directed therapies for cancer.
Keywords:	Cell Nucleus, Circular DNA, Genomic Instability, Human Chromosomes, Human Genome, Neoplasms, Neoplastic Gene Expression Regulation, Oncogenes
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Volume:	54
Number:	2
Page Range:	107-114
Date:	February 2022
Official Publication:	https://doi.org/10.1038/s41588-021-01000-z
PubMed:	View item in PubMed

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