Document Type
Article
Publication Date
12-16-2022
Publication Title
Biochemical Society transactions
Keywords
JGM, Humans, Oncogenes, Neoplasms, Genomics, DNA, Circular, DNA, Drug Resistance
JAX Source
Biochem Soc Trans. 2022;50(6):1911-20.
Volume
50
Issue
6
First Page
1911
Last Page
1920
ISSN
1470-8752
PMID
36355400
DOI
https://doi.org/10.1042/BST20221045
Abstract
The genome of cancer cells contains circular extrachromosomal DNA (ecDNA) elements not found in normal cells. Analysis of clinical samples reveal they are common in most cancers and their presence indicates poor prognosis. They often contain enhancers and driver oncogenes that are highly expressed. The circular ecDNA topology leads to an open chromatin conformation and generates new gene regulatory interactions, including with distal enhancers. The absence of centromeres leads to random distribution of ecDNAs during cell division and genes encoded on them are transmitted in a non-mendelian manner. ecDNA can integrate into and exit from chromosomal DNA. The numbers of specific ecDNAs can change in response to treatment. This dynamic ability to remodel the cancer genome challenges long-standing fundamentals, providing new insights into tumor heterogeneity, cancer genome remodeling, and drug resistance.
Recommended Citation
Pecorino L,
Verhaak R,
Henssen A,
Mischel P.
Extrachromosomal DNA (ecDNA): an origin of tumor heterogeneity, genomic remodeling, and drug resistance. Biochem Soc Trans. 2022;50(6):1911-20.
Comments
This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND).