Publisher Correction: Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma

Koche, Richard P.; Rodríguez-Fos, Elias; Helmsauer, Konstantin; Burkert, Martin; MacArthur, Ian; Mååg, Jesper L.V.; Chamorro, Rocio; Munoz-Perez, Natalia; Puiggròs, Montserrat; García, Heathcliff Dorado; Bei, Yi; Röefzaad, Claudia; Bardinet, Victor; Szymansky, Annabell; Winkler, Annika; Thole, Theresa; Timme, Natalie; Kasack, Katharina; Fuchs, Steffen; Klironomos, Filippos; Thiessen, Nina; Blanc, Eric; Schmelz, Karin; Künkele, Annette; Hundsdörfer, Patrick; Rosswog, Carolina; Theißen, Jessica; Beule, Dieter; Deubzer, Hedwig E.; Sauer, Sascha; Toedling, Joern; Fischer, Matthias; Hertwig, Falk; Schwarz, Roland F.; Eggert, Angelika; Torrents, David; Schulte, Johannes H.; Henssen, Anton

doi:10.1038/s41588-020-0598-1

Cited by 12 publications

(14 citation statements)

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“…HPV-containing ecDNAs as identified here are analogous to those observed in neuroblastoma (31), glioma (32) and other cancers. The ecDNAs in HPV-negative cancer types of course lack HPV sequences and frequently comprise very large (>1 megabase pair) circles.…”

Section: Discussionsupporting

confidence: 71%

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Intratumoral heterogeneity and clonal evolution induced by HPV integration

Akagi

Symer

Mahmoud

et al. 2022

Preprint

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The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. Continuous long-read sequencing of oropharyngeal cancers and cancer cell lines revealed interrelated but heterogeneous genomic structures comprising repetitive patterns of concatemerized virus and host segments. Evidence of this novel form of structural variation -- termed "circacatena" here -- was detected in extrachromosomal and intrachromosomal DNA and at chromosomal rearrangements. Unique breakpoint sequences shared across structurally diverse virus-host concatemers facilitated stepwise reconstruction of their evolution from common molecular ancestors. This analysis revealed that concatemerized HPV genomes are unstable and, upon insertion into and excision from chromosomes, facilitate capture, rearrangement, and rolling-circle amplification of host DNA. The data indicate that circacatena is driven by the dynamic, aberrant replication and recombination of an oncogenic DNA virus, thereby extending known consequences of HPV integration to include promotion of intratumoral heterogeneity and clonal evolution.

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Section: Discussionsupporting

confidence: 71%

“…Such ecDNAs can increase intratumoral heterogeneity and facilitate rapid adaptation to selective environmental pressures. This is attributed to unequal replication and segregation of ecDNAs in daughter cells during mitosis (31,32,34,35). Such ecDNA presence has been linked with poorer survival (36).…”

Section: Discussionmentioning

confidence: 99%

Intratumoral heterogeneity and clonal evolution induced by HPV integration

Akagi

Symer

Mahmoud

et al. 2022

Preprint

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“…Since focal amplifications and ecDNA can be identified from WGS data using amplification region reconstruction tool, AmpliconArchitect (AA) 2 , 4 – 7 , 9 , 30 , we first performed WGS of 36 pairs of GCA tumor and tumor-adjacent normal tissue from a high incidence GCA rate region in the northern region of China, Henan Province (see “Methods” section). All of our WGS data in 36 pairs of samples had sufficient sequencing coverage and a high mapping rate (>95% mapping rate) (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The difference in the fine structure from WGS and Circle-seq likely reflects the technical bias of the ecDNA amplicon prediction from the WGS and library preparation from the Circle-seq. Furthermore, we separated the list of circular DNA elements from Circle-seq data into ecDNA (copy number ≥ 7) and extrachromosomal circular DNA (eccDNA) (copy number < 7) following previous report 44 (Fig. 2c ).…”

Section: Resultsmentioning

confidence: 99%

“…Extrachromosomal DNA (ecDNA) was first identified more than half a century ago 1 , and has been associated with genomic instability 2 , 3 . With next-generation sequencing technologies and high throughput imaging platforms, an increasing number of studies have shown that ecDNAs are present in most tissues, and contribute to the intratumoral heterogeneity and cancer progression 2 , 4 – 9 . Using computational analysis of whole-genome sequencing (WGS) data from a large-scale cancer cohort, it has been demonstrated that the presence of ecDNA is cancer-type specific, and is associated with oncogene amplification and poor outcomes across multiple cancers 7 .…”

Section: Introductionmentioning

confidence: 99%

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Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma

et al. 2021

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The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.

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Extrachromosomal circular DNA (eccDNA): from carcinogenesis to drug resistance

Li,

Qian

2024

Clin Exp Med

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Extrachromosomal circular DNA (eccDNA) is a circular form of DNA that exists outside of the chromosome. Although it has only been a few decades since its discovery, in recent years, it has been found to have a close relationship with cancer, which has attracted widespread attention from researchers. Thus far, under the persistent research of researchers from all over the world, eccDNA has been found to play an important role in a variety of tumors, including breast cancer, lung cancer, ovarian cancer, etc. Herein, we review the sources of eccDNA, classifications, and the mechanisms responsible for their biogenesis. In addition, we introduce the relationship between eccDNA and various cancers and the role of eccDNA in the generation and evolution of cancer. Finally, we summarize the research significance and importance of eccDNA in cancer, and highlight new prospects for the application of eccDNA in the future detection and treatment of cancer.

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Publisher Correction: Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma

Abstract: In the version of the paper initially published, funding information for author Zsuzsanna Izsvák was missing. The Acknowledgements should have included the sentence 'Z.I. is funded by European Research Council-2011-ADG-TRANSPOSOstress-294742' .

Cited by 12 publications

References 0 publications

Intratumoral heterogeneity and clonal evolution induced by HPV integration

Intratumoral heterogeneity and clonal evolution induced by HPV integration

Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma

Extrachromosomal circular DNA (eccDNA): from carcinogenesis to drug resistance

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