Review
Classification of extrachromosomal circular DNA with a focus on the role of extrachromosomal DNA (ecDNA) in tumor heterogeneity and progression

https://doi.org/10.1016/j.bbcan.2020.188392Get rights and content
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Abstract

Although the eukaryotic genome is mainly comprised of linear chromosomal DNA, genes can also be found outside of chromosomes. The unconventional presence of extrachromosomal genes is usually found to be circular, and these structures are named extrachromosomal circular DNA (eccDNA), which are often observed in cancer cells. Various types of eccDNA including small polydispersed DNA (spcDNA), telomeric cirlces, microDNA, etc. have been discovered. Among these eccDNA, extrachromosomal DNA (ecDNA), which encompasses the full spectrum of large, gene-containing extrachromosomal particles, has regained great research interest due to recent technological advances such as next-generation sequencing and super-resolution microscopy. In this review, we summarize the different types of eccDNA and discuss the role of eccDNA, especially ecDNA in tumor heterogeneity and progression. Additionally, we discuss some possible future investigative directions related to ecDNA biogenesis and its clinical application.

Keywords

eccDNA
Extrachromosomal DNA
Biogenesis
Oncogene amplification
Micronuclei
Tumor heterogeneity

Abbreviations

eccDNA
extrachromosomal circular DNA
spcDNA
small polydispersed DNA
bp
base pairs
t-circles
telomeric circles
ecDNA
extrachromosomal DNA
DMs
double minutes
ALT
alternative lengthening of telomeres
ORC
origin recognition complex
WRN
Werner syndrome protein
HSRs
homogeneously staining regions
GBM
glioblastoma
FISH
fluorescent in situ hybridization
DHFR
dihydrofolate reductase
MTX
methotrexate
EGFR
epidermal growth factor receptor
TKI
tyrosine kinase inhibitor
BFB
Breakage-fusion-bridge
HU
Hydroxyurea
HBV
hepatitis B virus
cccDNA
covalently closed circular DNA
ctDNA
circulating tumor DNA

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1

ZL and WJ contributed equally to this work.