ArticleCell2019
Functional Enhancers Shape Extrachromosomal Oncogene Amplifications.
Abstract read
In one paragraph
Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers.
0numbers the graph read from it
0cells of the map it votes in
220citing papers in PubMed
–field-weighted citation impact
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.
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.
Who cites it
220 citing papers in PubMed.
- Micronuclear ecDNA constrains tumor cell fitness and is associated with favorable patient survival.Nature genetics · 2026Article
- Tumor-specific super-enhancer drives overexpression of EVI1/MECOM in ovarian cancer.Neoplasia (New York, N.Y.) · 2026Article
- Extrachromosomal DNA as a platform for epigenetic reprogramming in cancer.Molecular cancer · 2026Review
- Plasticity of extrachromosomal DNA segregation during drug adaptation.Nature communications · 2026Article
- Phase separation of ecDNA condensates establishes in-trans contact domains that boost selective MYC regulatory interactions.Nature communications · 2026Article
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Beyond chromosomes: exploring the diverse functions of extrachromosomal circular DNA.Journal of advanced research · 2026Review
- Extrachromosomal DNA Amplification as a Prognostic Factor for Cancer.Journal of personalized medicine · 2026Review
- Deciphering the role of cell-free extrachromosomal circular DNA in human heart failure.Human genomics · 2026Article
- 3D chromatin architecture in cancer: mechanisms of dysregulation and emerging therapeutic strategies.Experimental & molecular medicine · 2026Review
- The potential clinical implications of extrachromosomal circular DNA as a biomarker.Genes & diseases · 2026Review
- The newfound relationship between extrachromosomal DNAs and excised signal circles.FEBS letters · 2026Review
- An EGFR co-amplified lncRNA HELDR promotes glioblastoma malignancy through KAT7-driven gene programs.Nature cell biology · 2026Article
- Targeting extrachromosomal DNA in human cancers.Nature reviews. Drug discovery · 2026Review
- Convergent evolution of complex structural variants drives therapy resistance in metastatic prostate cancer.Genome biology · 2026Article
- BRCA1-A and LIG4 complexes mediate ecDNA biogenesis and cancer drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- AP-1 promotes oncogenic transcription in lung cancer cells by bridging promoter-enhancer interactions.Cancer gene therapy · 2026Article
- DeepECC: a deep learning framework for genome-wide identification and analysis of human cancer eccDNAs.Nucleic acids research · 2026Article
- Extrachromosomal circular DNA: a potential clinical therapeutic target in malignant tumors.Cellular & molecular biology letters · 2026Review
- Circulating extrachromosomal circular DNA as a prognostic biomarker for colorectal cancer.Cell communication and signaling : CCS · 2026Article
160 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
19 authors.
Andrew R MortonDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Nergiz Dogan-ArtunPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Zachary J FaberDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Graham MacLeodLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada.
Cynthia F BartelsDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Megan S PiazzaCenter for Human Genetics Laboratory, University Hospitals, Cleveland, OH 44106, USA.
Kevin C AllanDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Stephen C MackDepartment of Pediatrics, Division of Hematology and Oncology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
Xiuxing WangDepartment of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Ryan C GimpleDepartment of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH 44120, USA.
Qiulian WuDepartment of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Brian P RubinDepartments of Anatomic Pathology and Molecular Genetics, Cleveland Clinic, Lerner Research Institute and Taussig Cancer Center, Cleveland, OH 44195, USA.
Shashirekha ShettyCenter for Human Genetics Laboratory, University Hospitals, Cleveland, OH 44106, USA.
Stephane AngersLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON M5G 0A4, Canada.
Peter B DirksDevelopmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Richard C SallariAxiotl Inc., Tucson, AZ 85701, USA.
Mathieu LupienPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Jeremy N RichDepartment of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA; Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA 92037, USA. Electronic address: drjeremyrich@gmail.com.
Peter C ScacheriDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, Cleveland, OH 44106, USA. Electronic address: pxs183@case.edu.
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4MInherited colorectal cancer risk variants: from association to biologyR01CA143237 · NCI · UNIVERSITY OF VIRGINIA · PI CASEY, GRAHAM · 2010 to 2020
$8.4MDynamic Complexity of Brain Tumor Stem Cells (R35CA197718)R35CA197718 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RICH, JEREMY N · 2015 to 2021
$6.4M(Epi)genetic Risk Architectures in Opioid Dependent BrainR01DA043980 · NIDA · CASE WESTERN RESERVE UNIVERSITY · PI AKBARIAN, SCHAHRAM, JOHNSON, ERIC OTTO · 2017 to 2021
$4.9MThe role of gene enhancer elements in colon cancerR01CA160356 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI TESAR, PAUL JOSEPH · 2012 to 2023
$3.6MBiology of Colorectal Cancer Risk EnhancersR01CA204279 · NCI · UNIVERSITY OF VIRGINIA · PI CASEY, GRAHAM, SCACHERI, PETER CHRISTOPHER · 2016 to 2020
$3.0MNRSA Training CoreTL1TR002549 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI HARDING, CLIFFORD V · 2018 to 2022
$2.9MClinical and Translational Science Collaborative of ClevelandTL1TR000441 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$2.8MTargeting Ferritin in GlioblastomaR01CA169117 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG, CONNOR, JAMES ROBERT · 2013 to 2017
$2.7MMetabolism Informs Intertumoral & Intratumoral HeterogeneityR01NS087913 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NAKANO, ICHIRO, RICH, JEREMY N · 2014 to 2018
$2.0MTargeting Brain Tumor Stem Cells Through Novel Therapeutic CombinationsR01CA154130 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI RICH, JEREMY N · 2010 to 2014
$1.9MRole of enhancer elements in regulating prometastatic transcriptional programs in osteosarcomaR01CA193677 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI SCACHERI, PETER CHRISTOPHER · 2016 to 2020
$1.8MNCATS NIH HHS TL1 TR000441NCATS NIH HHS TL1 TR002549NCI NIH HHS F30 CA236313NCI NIH HHS R01 CA143237NCI NIH HHS R01 CA154130NCI NIH HHS R01 CA160356NCI NIH HHS R01 CA169117NCI NIH HHS R01 CA171652NCI NIH HHS R01 CA193677NCI NIH HHS R01 CA204279NCI NIH HHS R35 CA197718NIDA NIH HHS R01 DA043980NIGMS NIH HHS T32 GM007250NINDS NIH HHS R01 NS087913NINDS NIH HHS R01 NS089272NINDS NIH HHS R01 NS103434
Abstract
Non-coding regions amplified beyond oncogene borders have largely been ignored. Using a computational approach, we find signatures of significant co-amplification of non-coding DNA beyond the boundaries of amplified oncogenes across five cancer types. In glioblastoma, EGFR is preferentially co-amplified with its two endogenous enhancer elements active in the cell type of origin. These regulatory elements, their contacts, and their contribution to cell fitness are preserved on high-level circular extrachromosomal DNA amplifications. Interrogating the locus with a CRISPR interference screening approach reveals a diversity of additional elements that impact cell fitness. The pattern of fitness dependencies mirrors the rearrangement of regulatory elements and accompanying rewiring of the chromatin topology on the extrachromosomal amplicon. Our studies indicate that oncogene amplifications are shaped by regulatory dependencies in the non-coding genome.
Indexed as
Enhancer Elements, GeneticGene AmplificationOncogenesAcetylationCell Line, TumorCell SurvivalChromatinChromosomes, HumanCRISPR-Cas SystemsDNA, NeoplasmErbB ReceptorsGenes, NeoplasmGenetic LociGlioblastomaHistonesHumansChromatinDNA, NeoplasmErbB ReceptorsHistonesdouble minuteEGFRenhancerepigeneticextrachromosomal DNAglioblastomaMYCMYCNoncogene amplification
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
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.