Evidence map›Paper›PMID 36253572›Full record

ArticleNature genetics2022

Targeted profiling of human extrachromosomal DNA by CRISPR-CATCH.

King L Hung, Jens Luebeck, Siavash R Dehkordi, Caterina I Colón, Rui Li, Ivy Tsz-Lo Wong, Ceyda Coruh, Prashanthi Dharanipragada, Shirley H Lomeli, Natasha E Weiser and 16 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
10.8field-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

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Targeting extrachromosomal DNA in human cancers.Nature reviews. Drug discovery · 2026
    Review
  13. Evolution of oncogene amplification across 86,000 cancer cell genomes.bioRxiv : the preprint server for biology · 2026
    Article
  14. Review
  15. Article
  16. Fast and accurate resolution of ecDNA sequence using Cycle-Extractor.bioRxiv : the preprint server for biology · 2026
    Article
  17. Article
  18. Review
  19. bioRxiv : the preprint server for biology · 2026
    Article
  20. Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 9 institutions in 3 countries.

King L HungCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3662-4662
Jens Luebeck *Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4391-979X
Siavash R Dehkordi *Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA.
Caterina I ColónCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Rui LiCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Ivy Tsz-Lo WongSarafan ChEM-H, Stanford University, Stanford, CA, USA.
Ceyda CoruhPlant Molecular and Cellular Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Prashanthi DharanipragadaDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Shirley H LomeliDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Natasha E WeiserCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-9971-2961
Gatien MoriceauDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Xiao ZhangDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-1706-2868
Chris BaileyCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Kathleen E HoulahanDepartment of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Wenting YangDepartment of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Rocío Chamorro GonzálezDepartment of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-5653-7259
Charles SwantonCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.ORCID http://orcid.org/0000-0002-4299-3018
Christina CurtisDepartment of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Mariam Jamal-HanjaniCancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK.ORCID http://orcid.org/0000-0003-1212-1259
Anton G HenssenDepartment of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-1534-778X
Julie A LawPlant Molecular and Cellular Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-7472-7753
William J GreenleafCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1409-3095
Roger S LoDivision of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-5337-5004
Paul S MischelSarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-4560-2211
Vineet BafnaDepartment of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-5810-6241
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA. howchang@stanford.edu.ORCID http://orcid.org/0000-0002-9459-4393
Stanford University · USUniversity of California, Los Angeles · USUniversity of California San Diego · USSalk Institute for Biological Studies · USUniversity College London Hospitals NHS Foundation Trust · GBCharité - Universitätsmedizin Berlin · DEGerman Cancer Research Center · DEHoward Hughes Medical Institute · USThe Francis Crick Institute · GB

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
VACCINE INDUCED IMMUNITY IN THE YOUNG AND AGEDU19AI057266 · NIAID · EMORY UNIVERSITY · PI Rafi Ahmed · 2003 to 2026
$81.7M
Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2014 to 2018
$15.2M
Center for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8M
Project 3: Modeling and overcoming resistance to melanoma immunotherapyP01CA244118 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RIBAS, ANTONI · 2020 to 2024
$12.8M
TARGETED COMBINATORIAL TREATMENT OF BRAF MELANOMASP01CA168585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LO, ROGER S · 2013 to 2017
$8.4M
LncRNA mechanisms in cancerR35CA209919 · NCI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2016 to 2022
$6.4M
Preventing MAPK inhibitor resistance in melanoma by targeting genomic instability and immune resistanceR01CA176111 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROGER S LO · 2013 to 2026
$5.4M
Establishment and Modulation of DNA Methylation Patterns in ArabidopsisR01GM112966 · NIGMS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI LAW, JULIE ANN · 2015 to 2024
$3.5M
Software and algorithms for elucidating the structure, function, and evolution of extrachromosomal DNAU24CA264379 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BAFNA, VINEET, MESIROV, JILL P. · 2021 to 2025
$3.5M
Computational methods for detecting patterns of complex genomic variationR01GM114362 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Vineet Bafna · 2016 to 2026
$3.1M
eDyNAmiC - UCSDOT2CA278635 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Vineet Bafna · 2022 to 2026
$1.8M
Cancer Research UK 17786Cancer Research UK 21999Cancer Research UK 30025Cancer Research UK CGCATF-2021/100012Howard Hughes Medical InstituteNCI NIH HHS F99 CA274692NCI NIH HHS OT2 CA278635NCI NIH HHS P01 CA168585NCI NIH HHS P01 CA244118NCI NIH HHS R01 CA176111NCI NIH HHS R35 CA209919NCI NIH HHS U24 CA264379NHGRI NIH HHS P50 HG007735NHGRI NIH HHS RM1 HG007735NIAID NIH HHS U19 AI057266NIGMS NIH HHS R01 GM112966NIGMS NIH HHS R01 GM114362Wellcome Trust FC001169Wellcome Trust FC001202
6 · The paper itself

Abstract

Extrachromosomal DNA (ecDNA) is a common mode of oncogene amplification but is challenging to analyze. Here, we adapt CRISPR-CATCH, in vitro CRISPR-Cas9 treatment and pulsed field gel electrophoresis of agarose-entrapped genomic DNA, previously developed for bacterial chromosome segments, to isolate megabase-sized human ecDNAs. We demonstrate strong enrichment of ecDNA molecules containing EGFR, FGFR2 and MYC from human cancer cells and NRAS ecDNA from human metastatic melanoma with acquired therapeutic resistance. Targeted enrichment of ecDNA versus chromosomal DNA enabled phasing of genetic variants, identified the presence of an EGFRvIII mutation exclusively on ecDNAs and supported an excision model of ecDNA genesis in a glioblastoma model. CRISPR-CATCH followed by nanopore sequencing enabled single-molecule ecDNA methylation profiling and revealed hypomethylation of the EGFR promoter on ecDNAs. We distinguished heterogeneous ecDNA species within the same sample by size and sequence with base-pair resolution and discovered functionally specialized ecDNAs that amplify select enhancers or oncogene-coding sequences.

Indexed as

GlioblastomaNeoplasmsDNAErbB ReceptorsHumansOncogenesDNAErbB Receptors

Identifiers

PMID36253572
PMCPMC9649439
OpenAlexW4306412179

What OpenQuestion holds

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LicenceCC BY
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.