ArticleNature communications2023
3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20citing papers in PubMed
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
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- Machine learning-predicted chromatin organization landscape across pediatric tumors.Scientific reports · 2026Article
- Enhancer-dependent gene regulation in space, time, and malignancies.International journal of cancer · 2026Review
- Profiling extracellular vesicles from cerebrospinal fluid for classification of intradural spinal tumors.Scientific reports · 2025Article
- Loss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth.Neuro-oncology · 2025Article
- Development and extensive sequencing of a broadly-consented Genome in a Bottle matched tumor-normal pair.Scientific data · 2025Article
- EpiSwitch PSE Blood Test Reduces Unnecessary Prostate Biopsies: A Real-World Clinical Utility Study.Cancers · 2025Article
- Development and extensive sequencing of a broadly-consented Genome in a Bottle matched tumor-normal pair.bioRxiv : the preprint server for biology · 2025Article
- Detection of Gene Fusions and Rearrangements in Formalin-Fixed, Paraffin-Embedded Solid Tumor Specimens Using High-Throughput Chromosome Conformation Capture.The Journal of molecular diagnostics : JMD · 2025Article
- Three-dimensional regulatory hubs support oncogenic programs in glioblastoma.Molecular cell · 2025Article
- Integrative cytogenetic and molecular studies unmask "chromosomal mimicry" in hematologic malignancies.Blood advances · 2025Article
- Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation.Frontiers in oncology · 2025Review
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- Epigenetic Regulation in Drosophila Tumor Models.Advances in experimental medicine and biology · 2025Review
- Three-dimensional regulatory hubs support oncogenic programs in glioblastoma.bioRxiv : the preprint server for biology · 2024Article
- Chromosome conformation capture technologies as tools to detect structural variations and their repercussion in chromatin 3D configuration.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
51 authors at 12 institutions in 4 countries.
Konstantin Okonechnikov *Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Aylin Camgöz *Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Owen ChapmanDivision of Genomics and Precision Medicine, Department of Medicine, University of California San Diego (UCSD), San Diego, USA.
Sameena WaniDivision of Genomics and Precision Medicine, Department of Medicine, University of California San Diego (UCSD), San Diego, USA.
Donglim Esther ParkDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, 92037, USA.
Jens-Martin HübnerHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Abhijit ChakrabortyCenters for Cancer Immunotherapy and Autoimmunity, La Jolla Institute for Immunology, La Jolla, CA, USA.ORCID 0000-0002-1500-3699
Meghana PagadalaDivision of Genomics and Precision Medicine, Department of Medicine, University of California San Diego (UCSD), San Diego, USA.
Rosalind BumpPeptide Biology Labs, Salk Institute for Biological Studies, La Jolla, CA, USA.
Sahaana ChandranPeptide Biology Labs, Salk Institute for Biological Studies, La Jolla, CA, USA.
Katerina KraftCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Rocio Acuna-HidalgoMax Planck Institute for Molecular Genetics, Berlin, Germany.
Derek ReidArima Genomics, Inc, San Diego, CA, 92121, USA.
Kristin SikkinkArima Genomics, Inc, San Diego, CA, 92121, USA.ORCID 0000-0002-0805-0622
Monika MauermannHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Edwin F JuarezDivision of Genomics and Precision Medicine, Department of Medicine, University of California San Diego (UCSD), San Diego, USA.
Anne JenseitHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
James T RobinsonDivision of Genomics and Precision Medicine, Department of Medicine, University of California San Diego (UCSD), San Diego, USA.
Kristian W PajtlerHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Till MildeHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.ORCID 0000-0002-7267-1052
Natalie JägerHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Petra FieselHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Ling MorganDivision of Genomics and Precision Medicine, Department of Medicine, University of California San Diego (UCSD), San Diego, USA.
Sunita SridharDivision of Genomics and Precision Medicine, Department of Medicine, University of California San Diego (UCSD), San Diego, USA.
Nicole G CoufalSanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA, 92037, USA.
Michael LevyNeurosurgery, University of California San Diego - Rady Children's Hospital, San Diego, CA, 92123, USA.ORCID 0000-0001-7545-8620
Denise MalickiPathology, University of California San Diego - Rady Children's Hospital, San Diego, CA, 92123, USA.
Charlotte HobbsRady Children's Institute for Genomic Medicine, San Diego, CA, 92123, USA.
Stephen KingsmoreRady Children's Institute for Genomic Medicine, San Diego, CA, 92123, USA.ORCID 0000-0001-7180-2527
Shareef NahasRady Children's Institute for Genomic Medicine, San Diego, CA, 92123, USA.
Matija SnuderlDepartment of Pathology, NYU Langone Health, NYU Grossman School of Medicine, 550 First Ave, New York, NY, 10016, USA.
John CrawfordDepartment of Neurosciences, University of California San Diego - Rady Children's Hospital, San Diego, CA, 92123, USA.
Robert J Wechsler-ReyaSanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA, 92037, USA.ORCID 0000-0002-7463-8352
Tom Belle DavidsonDivision of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-1655-3860
Jennifer CotterDivision of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-1420-3314
George MichaielDivision of Hematology-Oncology, Cancer and Blood Disease Institute and Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.
Gudrun FleischhackGerman Cancer Consortium (DKTK), West German Cancer Center, Pediatrics III, University Hospital Essen, Essen, Germany.ORCID 0000-0001-5714-007X
Stefan MundlosMax Planck Institute for Molecular Genetics, Berlin, Germany.ORCID 0000-0002-9788-3166
Anthony SchmittArima Genomics, Inc, San Diego, CA, 92121, USA.
Hannah CarterDivision of Genomics and Precision Medicine, Department of Medicine, University of California San Diego (UCSD), San Diego, USA.
Kulandaimanuvel Antony MichealrajDivision of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Center, Hospital for Sick Children, University of Toronto, Toronto, ONT, Canada.
Sachin A KumarDivision of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Center, Hospital for Sick Children, University of Toronto, Toronto, ONT, Canada.ORCID 0000-0002-4853-3864
Michael D TaylorDivision of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Center, Hospital for Sick Children, University of Toronto, Toronto, ONT, Canada.ORCID 0000-0001-7009-3466
Jeremy RichDivision of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, 92037, USA.
Frank BuchholzNational Center for Tumor Diseases (NCT): German Cancer Research Center (DKFZ) Heidelberg, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.ORCID 0000-0002-4577-3344
Jill P MesirovDivision of Genomics and Precision Medicine, Department of Medicine, University of California San Diego (UCSD), San Diego, USA.
Stefan M PfisterHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Ferhat AyCenters for Cancer Immunotherapy and Autoimmunity, La Jolla Institute for Immunology, La Jolla, CA, USA.ORCID 0000-0002-0708-6914
Jesse R DixonPeptide Biology Labs, Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID 0000-0002-6273-2181
Marcel KoolHopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Lukas ChavezDivision of Genomics and Precision Medicine, Department of Medicine, University of California San Diego (UCSD), San Diego, USA. lukaschavez@health.ucsd.edu.ORCID 0000-0002-8718-8848
University of California San Diego · USGerman Cancer Research Center · DEChildren’s Institute · USArima Genomics (United States) · USChildren's Hospital of Los Angeles · USSalk Institute for Biological Studies · USUniversity of Toronto · CALa Jolla Institute for Immunology · USMax Planck Institute for Molecular Genetics · DENYU Langone Health · USSanford Burnham Prebys Medical Discovery Institute · USStanford University · US
Funding
San Diego Biomedical Informatics Education & Research (SABER)T15LM011271 · NLM · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHAMIM NEMATI · 2012 to 2026
$9.7MSupporting Integrative Genomic Analysis Users with GenePatternR01GM074024 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MESIROV, JILL P. · 2005 to 2019
$6.6MA Rational Systematic Approach to Find Combinations of Pharmacologic and Immune Therapies that Target Identifiable Oncogenic StatesU01CA217885 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COHEN, EZRA, KAUFMAN, DAN S. · 2017 to 2021
$5.1MThe Integrative Genomics Viewer (IGV) for Cancer ResearchU24CA258406 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JILL P. MESIROV, James Thomas Robinson · 2021 to 2026
$5.1MThe Integrative Genomics Viewer (IGV): visualization supporting cancer researchU24CA210004 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MESIROV, JILL P., ROBINSON, JAMES THOMAS · 2016 to 2020
$3.8MEmbryonal Brain Tumor NetworksU01CA184898 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI FRAENKEL, ERNEST, MESIROV, JILL P. · 2014 to 2019
$3.6MMechanisms of formation of 3D genome structuresDP5OD023071 · OD · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI DIXON, JESSE R · 2016 to 2020
$2.4MTranscriptional activation of RCOR2 as a novel oncogenic mechanism in supratentorial ependymomaR21NS130137 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI CHAVEZ, LUKAS · 2022 to 2022
$536kTranscriptional activation of LAMC1 as a resistance mechanism in recurrent PFA EpendymomaR21NS120075 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHAVEZ, LUKAS · 2021 to 2022
$471kDisruption of a DNA loop as a complementary mechanism of H3.3K27M mutationsR21NS116455 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHAVEZ, LUKAS · 2020 to 2021
$438kNCI NIH HHS U01 CA184898NCI NIH HHS U01 CA217885NCI NIH HHS U24 CA210004NCI NIH HHS U24 CA258406NIGMS NIH HHS R01 GM074024NIH HHS DP5 OD023071NINDS NIH HHS R21 NS116455NINDS NIH HHS R21 NS120075NINDS NIH HHS R21 NS130137NLM NIH HHS T15 LM011271
Abstract
Ependymoma is a tumor of the brain or spinal cord. The two most common and aggressive molecular groups of ependymoma are the supratentorial ZFTA-fusion associated and the posterior fossa ependymoma group A. In both groups, tumors occur mainly in young children and frequently recur after treatment. Although molecular mechanisms underlying these diseases have recently been uncovered, they remain difficult to target and innovative therapeutic approaches are urgently needed. Here, we use genome-wide chromosome conformation capture (Hi-C), complemented with CTCF and H3K27ac ChIP-seq, as well as gene expression and DNA methylation analysis in primary and relapsed ependymoma tumors, to identify chromosomal conformations and regulatory mechanisms associated with aberrant gene expression. In particular, we observe the formation of new topologically associating domains ('neo-TADs') caused by structural variants, group-specific 3D chromatin loops, and the replacement of CTCF insulators by DNA hyper-methylation. Through inhibition experiments, we validate that genes implicated by these 3D genome conformations are essential for the survival of patient-derived ependymoma models in a group-specific manner. Thus, this study extends our ability to reveal tumor-dependency genes by 3D genome conformations even in tumors that lack targetable genetic alterations.
Indexed as
EpendymomaNeoplasm Recurrence, LocalChildChild, PreschoolChromatinChromosome MappingChromosomesGenomeHumansChromatin
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