Extrachromosomal circular DNA in cancer: history, current knowledge, and methods

Noer, Julie B.; Hørsdal, Oskar K.; Xiang, Xi; Luo, Yonglun; Regenberg, Birgitte

doi:10.1016/j.tig.2022.02.007

Cited by 72 publications

(74 citation statements)

References 104 publications

(228 reference statements)

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“…Recent studies have shown that circular DNA is prevalent in human tissues and can be identified by several strategies 4,24 . AA algorithm reconstructs the structure of focally amplified regions using whole-genome sequencing (WGS) data 1 ; this approach could detect a large tumor-specific circular DNA catalog that showed a preference of long circle length (>1,000bp).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…With the rapid development of sequencing and imaging technology, circular DNA was broadly identified in normal tissues and cancer 1,2 , and thereby is gaining substantial attention from biological and clinical researchers in recent years 3,4 . Circular DNA is commonly recognized in two independent classes: (1) large size and copy number–amplified extrachromosomal circular DNA (referred to ecDNA); (2) small extrachromosomal circular DNA (including microDNA; referred to eccDNA).…”

Section: Introductionmentioning

confidence: 99%

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ScanTecc classifies primary cancers via cell-free extrachromosomal circular DNA in peripheral blood

Fang

Wang

et al. 2022

Preprint

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Extrachromosomal circular DNA (eccDNA) is gaining substantial attention in basic and clinical research for its contribution to tumor heterogeneity, biogenesis, and evolution. However, its presence and molecular features in peripheral blood from cancer patients are poorly understood. Here, we demonstrated the existence of eccDNA molecules in cancer patients’ plasma using atomic-force microscopy and high throughput sequencing technology. We then developed a method named ScanTecc (Screening cancer Types with cell-free eccDNA) that integrates cell-free circular DNA sequencing and machine learning approaches for cancer patient screening and classification. We applied ScanTecc on a total of 413 patients with multiple types of human primary cancers and 52 healthy individuals and found a significantly greater number and more extended size of eccDNAs in patients’ peripheral blood. ScanTecc accurately distinguished cancer patients (including early stages I and II) from healthy individuals with an overall prediction rate of 0.85 and identified distinct cancer types with an overall prediction rate of 0.84. Our study provides evidence for a non-invasive approach potentially applicable for early detection of cancer patients in clinics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ScanTecc classifies primary cancers via cell-free extrachromosomal circular DNA in peripheral blood

Fang

Wang

et al. 2022

Preprint

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“…Whilst the synthetic GAP1 locus was designed and generated as part of the synXI construction process, synthetic loci allowing generation of SPeccs analogous to other eccDNAs would not require full synthetic chromosomes to be exploited. Given the emerging importance of eccDNAs in the fields of evolution, immunology (Wang et al, 2021), cancer (Ling et al, 2021;Noer et al, 2022) and aging (Hull et al, 2019), we believe that the SPecc methodology will be a valuable tool for a wide range of future studies, both in yeast and in other organisms. SPeccs may also be promising new tools for fields such as synthetic biology and biotechnology.…”

Section: Discussionmentioning

confidence: 99%

Synthetic yeast chromosome XI design enables extrachromosomal circular DNA formation on demand

Blount

Driessen

et al. 2022

Preprint

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We describe construction of the 660 kilobase synthetic yeast chromosome XI (synXI) and reveal how synthetic redesign of non-coding DNA elements impact the cell. To aid construction from synthesized 5 to 10 kilobase DNA fragments, we implemented CRISPR-based methods for synthetic crossovers in vivo and used these methods in an extensive process of bug discovery, redesign and chromosome repair, including for the precise removal of 200 kilobases of unexpected repeated sequence. In synXI, the underlying causes of several fitness defects were identified as modifications to non-coding DNA, including defects related to centromere function and mitochondrial activity that were subsequently corrected. As part of synthetic yeast chromosome design, loxPsym sequences for Cre-mediated recombination are inserted between most genes. Using the GAP1 locus from chromosome XI, we show here that targeted insertion of these sites can be used to create extrachromosomal circular DNA on demand, allowing direct study of the effects and propagation of these important molecules. Construction and characterization of synXI has uncovered effects of non-coding and extrachromosomal circular DNA, contributing to better understanding of these elements and informing future synthetic genome design.

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“…With such a high potential for circle formation, megabase sized circles are expected to appear. In human cancers, megabase sized ecDNA that contain oncogenes are identified through whole-genome sequencing and FISH microscopy [8,14,28]. The lack of large 4 circles in the studies where eccDNA is isolated from sperm, could therefore be due to technical limitations such as breakage of the large DNA molecules before exonuclease treatment or unspecific cutting with restriction enzymes to remove linear and mitochondrial DNA.…”

Section: I) Circular Dna In Mammalian Germlinesmentioning

confidence: 99%

Did circular DNA shape the evolution of mammalian genomes?

Holt

Tane

Regenberg

2022

Preprint

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Extrachromosomal circular DNA of chromosomal origin (eccDNA) can rapidly shape the evolution and adaptation of mitotically dividing cells such as tumor cells. However, whether eccDNA has a permanent impact on genome evolution through the germline is largely unexplored. Here, we propose that a large fraction of the syntenic changes that are found between mammalian species are caused by germline transposition of eccDNA. We have previously shown the existence of eccDNA in mammalian meiotic cells. By reanalysis of available synteny maps, we now find that up to 6% of mammalian genomes might have rearranged via a circular DNA intermediate. Hence, eccDNA in the germline is expected to have large effects on evolution of gene order.

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Extrachromosomal circular DNA in cancer: history, current knowledge, and methods

Cited by 72 publications

References 104 publications

ScanTecc classifies primary cancers via cell-free extrachromosomal circular DNA in peripheral blood

ScanTecc classifies primary cancers via cell-free extrachromosomal circular DNA in peripheral blood

Synthetic yeast chromosome XI design enables extrachromosomal circular DNA formation on demand

Did circular DNA shape the evolution of mammalian genomes?

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