Guilt by association: EcDNA as a mobile transactivator in cancer.

Document Type

Article

Publication Date

9-1-2022

Publication Title

Trends Cancer

Keywords

JGM, Chromatin, DNA, Circular, DNA, Mitochondrial, Humans, Neoplasms, Oncogenes, Trans-Activators

JAX Source

Trends Cancer. 2022;8(9):747-58.

Volume

8

Issue

9

First Page

747

Last Page

758

ISSN

2405-8025

PMID

35753910

DOI

https://doi.org/10.1016/j.trecan.2022.04.011

Grant

C-L.W. is supported by 4DN (U54 DK107967), R01 GM127531, and the ENCODE (UM1 HG009409) consortia, and National Cancer Institute awards (P30CA034196 and R33 CA236681) from the US National Institutes of Health.

Abstract

Extrachromosomal DNA (ecDNA), first described in the 1960s, is emerging as a prevalent but poorly characterized oncogenic alteration in cancer. ecDNA is a reservoir for oncogene amplification and is associated with an aggressive tumor phenotype and poor patient outcome. Despite the long-held knowledge of its existence, little is known about how ecDNA affects tumor cell behavior. Recent data reveal that ecDNA hubs are mobile transcriptional enhancers which can transactivate gene expression through chromatin interactions. Given its prevalence, structural complexity, and unequal segregation into daughter cells, ecDNA can offer selective growth advantages, contribute to intratumor heterogeneity (ITH), and accelerate tumor evolution. Future technology development is expected to transform the current paradigm for studying ecDNA and lead to therapeutic strategies targeting ecDNA vulnerabilities.

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