Evidence map›Paper›PMID 34819316›Full record

ArticleCancer discovery2022

Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer.

Eunhee Yi, Amit D Gujar, Molly Guthrie, Hoon Kim, Dacheng Zhao, Kevin C Johnson, Samirkumar B Amin, Megan L Costa, Qianru Yu, Sunit Das and 4 more

Open access · greenAbstract read
In one paragraph

Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 1 pooled it
8.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.

  1. Pooled it
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  14. Targeting extrachromosomal DNA in human cancers.Nature reviews. Drug discovery · 2026
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  20. bioRxiv : the preprint server for biology · 2026
    Article

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 5 countries.

Eunhee YiThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.ORCID 0000-0002-7839-7795
Amit D GujarThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.ORCID 0000-0003-0689-6680
Molly GuthrieThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
Hoon KimThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
Dacheng ZhaoThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
Kevin C JohnsonThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
Samirkumar B AminThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.ORCID 0000-0002-3207-9505
Megan L CostaThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.ORCID 0000-0001-5172-6782
Qianru YuThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
Sunit DasArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for SickKids, University of Toronto, Toronto, Canada.ORCID 0000-0002-2146-4168
Nathaniel JilletteThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
Patricia A ClowThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.ORCID 0000-0003-3669-7826
Albert W ChengThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut. roel.verhaak@jax.org albert.cheng@jax.org.ORCID 0000-0003-2653-5743
Roel G W VerhaakThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut. roel.verhaak@jax.org albert.cheng@jax.org.ORCID 0000-0003-2773-0436
Jackson Laboratory · USAmsterdam Neuroscience · NLSt. Michael's Hospital · CA

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9M
Modular Platform for Combinatorial Epigenome ManipulationR01HG009900 · NHGRI · JACKSON LABORATORY · PI ADAMS, MARK D · 2018 to 2022
$3.7M
Extrachromosomal DNA as a Targetable Mechanism in GlioblastomaR01CA237208 · NCI · YALE UNIVERSITY · PI VERHAAK, ROEL GW · 2020 to 2024
$2.5M
Advancing Ultra Long-read Sequencing and Chromatin Interaction Analyses for Chromosomal and Extrachromosomal Structural Variation Characterization in CancerR33CA236681 · NCI · JACKSON LABORATORY · PI VERHAAK, ROEL GW, WEI, CHIA-LIN · 2020 to 2020
$1.4M
Modeling Tumor Evolution in GliomaR21NS114873 · NINDS · JACKSON LABORATORY · PI VERHAAK, ROEL GW · 2019 to 2020
$520k
Characterization of extrachromosomal DNAs in tumors through computational analysis of single-cell and bulk sequencing dataR21CA256575 · NCI · YALE UNIVERSITY · PI VERHAAK, ROEL GW · 2021 to 2021
$478k
NCI NIH HHS P30 CA034196NCI NIH HHS R01 CA237208NCI NIH HHS R21 CA256575NCI NIH HHS R33 CA236681NHGRI NIH HHS R01 HG009900NINDS NIH HHS R21 NS114873
6 · The paper itself

Abstract

Oncogenic extrachromosomal DNA elements (ecDNA) play an important role in tumor evolution, but our understanding of ecDNA biology is limited. We determined the distribution of single-cell ecDNA copy number across patient tissues and cell line models and observed how cell-to-cell ecDNA frequency varies greatly. The exceptional intratumoral heterogeneity of ecDNA suggested ecDNA-specific replication and propagation mechanisms. To evaluate the transfer of ecDNA genetic material from parental to offspring cells during mitosis, we established the CRISPR-based ecTag method. ecTag leverages ecDNA-specific breakpoint sequences to tag ecDNA with fluorescent markers in living cells. Applying ecTag during mitosis revealed disjointed ecDNA inheritance patterns, enabling rapid ecDNA accumulation in individual cells. After mitosis, ecDNAs clustered into ecDNA hubs, and ecDNA hubs colocalized with RNA polymerase II, promoting transcription of cargo oncogenes. Our observations provide direct evidence for uneven segregation of ecDNA and shed new light on mechanisms through which ecDNAs contribute to oncogenesis. SIGNIFICANCE: ecDNAs are vehicles for oncogene amplification. The circular nature of ecDNA affords unique properties, such as mobility and ecDNA-specific replication and segregation behavior. We uncovered fundamental ecDNA properties by tracking ecDNAs in live cells, highlighting uneven and random segregation and ecDNA hubs that drive cargo gene transcription.

Indexed as

Extrachromosomal InheritanceGene AmplificationTumor MicroenvironmentDNAHumansNeoplasmsDNA

Identifiers

PMID34819316
PMCPMC8831456
OpenAlexW3216681490

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.