Your browser doesn't support javascript.
loading
Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma.
Chapman, Owen S; Luebeck, Jens; Sridhar, Sunita; Wong, Ivy Tsz-Lo; Dixit, Deobrat; Wang, Shanqing; Prasad, Gino; Rajkumar, Utkrisht; Pagadala, Meghana S; Larson, Jon D; He, Britney Jiayu; Hung, King L; Lange, Joshua T; Dehkordi, Siavash R; Chandran, Sahaana; Adam, Miriam; Morgan, Ling; Wani, Sameena; Tiwari, Ashutosh; Guccione, Caitlin; Lin, Yingxi; Dutta, Aditi; Lo, Yan Yuen; Juarez, Edwin; Robinson, James T; Korshunov, Andrey; Michaels, John-Edward A; Cho, Yoon-Jae; Malicki, Denise M; Coufal, Nicole G; Levy, Michael L; Hobbs, Charlotte; Scheuermann, Richard H; Crawford, John R; Pomeroy, Scott L; Rich, Jeremy N; Zhang, Xinlian; Chang, Howard Y; Dixon, Jesse R; Bagchi, Anindya; Deshpande, Aniruddha J; Carter, Hannah; Fraenkel, Ernest; Mischel, Paul S; Wechsler-Reya, Robert J; Bafna, Vineet; Mesirov, Jill P; Chavez, Lukas.
Afiliação
  • Chapman OS; Bioinformatics and Systems Biology Graduate Program, University of California San Diego, San Diego, CA, USA.
  • Luebeck J; Department of Medicine, University of California San Diego, San Diego, CA, USA.
  • Sridhar S; Sanford Burnham Prebys Medical Discovery Institute, San Diego, CA, USA.
  • Wong IT; Bioinformatics and Systems Biology Graduate Program, University of California San Diego, San Diego, CA, USA.
  • Dixit D; Department of Computer Science and Engineering, University of California San Diego, San Diego, CA, USA.
  • Wang S; Department of Medicine, University of California San Diego, San Diego, CA, USA.
  • Prasad G; Department of Pediatrics, UC San Diego and Rady Children's Hospital, San Diego, CA, USA.
  • Rajkumar U; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Pagadala MS; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • Larson JD; Sanford Burnham Prebys Medical Discovery Institute, San Diego, CA, USA.
  • He BJ; Department of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
  • Hung KL; Department of Computer Science and Engineering, University of California San Diego, San Diego, CA, USA.
  • Lange JT; Department of Computer Science and Engineering, University of California San Diego, San Diego, CA, USA.
  • Dehkordi SR; Department of Computer Science and Engineering, University of California San Diego, San Diego, CA, USA.
  • Chandran S; Medical Scientist Training Program, University of California San Diego, San Diego, CA, USA.
  • Adam M; Biomedical Sciences Graduate Program, University of California San Diego, San Diego, CA, USA.
  • Morgan L; Sanford Burnham Prebys Medical Discovery Institute, San Diego, CA, USA.
  • Wani S; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
  • Tiwari A; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
  • Guccione C; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Lin Y; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
  • Dutta A; Department of Computer Science and Engineering, University of California San Diego, San Diego, CA, USA.
  • Lo YY; Salk Institute for Biological Studies, La Jolla, CA, USA.
  • Juarez E; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Robinson JT; Department of Medicine, University of California San Diego, San Diego, CA, USA.
  • Korshunov A; Sanford Burnham Prebys Medical Discovery Institute, San Diego, CA, USA.
  • Michaels JA; Sanford Burnham Prebys Medical Discovery Institute, San Diego, CA, USA.
  • Cho YJ; Bioinformatics and Systems Biology Graduate Program, University of California San Diego, San Diego, CA, USA.
  • Malicki DM; Department of Medicine, University of California San Diego, San Diego, CA, USA.
  • Coufal NG; Department of Computer Science and Engineering, University of California San Diego, San Diego, CA, USA.
  • Levy ML; Department of Computer Science and Engineering, University of California San Diego, San Diego, CA, USA.
  • Hobbs C; Sanford Burnham Prebys Medical Discovery Institute, San Diego, CA, USA.
  • Scheuermann RH; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital and Healthcare Center, San Diego, CA, USA.
  • Crawford JR; Department of Medicine, University of California San Diego, San Diego, CA, USA.
  • Pomeroy SL; Department of Medicine, University of California San Diego, San Diego, CA, USA.
  • Rich JN; Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 280, Heidelberg, Germany.
  • Zhang X; Papé Pediatric Research Institute, Department of Pediatrics and Knight Cancer Insitute, Oregon Health and Sciences University, Portland, OR, USA.
  • Chang HY; Papé Pediatric Research Institute, Department of Pediatrics and Knight Cancer Insitute, Oregon Health and Sciences University, Portland, OR, USA.
  • Dixon JR; Division of Pathology, UC San Diego and Rady Children's Hospital, San Diego, CA, USA.
  • Bagchi A; Department of Pediatrics, UC San Diego and Rady Children's Hospital, San Diego, CA, USA.
  • Deshpande AJ; Division of Pathology, UC San Diego and Rady Children's Hospital, San Diego, CA, USA.
  • Carter H; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital and Healthcare Center, San Diego, CA, USA.
  • Fraenkel E; J. Craig Venter Institute, La Jolla, CA, USA.
  • Mischel PS; Department of Pathology, University of California San Diego, San Diego, CA, USA.
  • Wechsler-Reya RJ; Department of Pediatrics, University of California Irvine and Children's Hospital Orange County, Irvine, CA, USA.
  • Bafna V; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Mesirov JP; Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
  • Chavez L; Harvard Medical School, Boston, MA, USA.
Nat Genet ; 55(12): 2189-2199, 2023 Dec.
Article em En | MEDLINE | ID: mdl-37945900
ABSTRACT
Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. A subset of tumors harbored multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging and CRISPR inhibition experiments in medulloblastoma models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative 'enhancer rewiring' events on ecDNA. This study reveals the frequency and diversity of ecDNA in medulloblastoma, stratified into molecular subgroups, and suggests copy number heterogeneity and enhancer rewiring as oncogenic features of ecDNA.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cerebelares / Meduloblastoma / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cerebelares / Meduloblastoma / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article