Childhood Cancer Data Initiative Annual Symposium (Abstract Registration): Submission #83

serial: '83'
sid: '193782'
uuid: ce8c5218-fc94-40e1-b0a2-67ebb733e588
uri: /nci/ccdisymposium/abstract
created: '1788478981'
completed: '1788479282'
changed: '1788479282'
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langcode: en
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data:
  authors_:
    - add_author_degree: Master
      add_author_first_name: Hui
      add_author_last_name: Hui
      add_author_middle: ''
      add_author_organization: 'University of California San Diego'
    - add_author_degree: Bachelor
      add_author_first_name: Jessica
      add_author_last_name: Wang
      add_author_middle: ''
      add_author_organization: 'Sanford Burnham Prebys Medical Discovery Institute'
    - add_author_degree: Bachelor
      add_author_first_name: Rishaan
      add_author_last_name: Kenkre
      add_author_middle: ''
      add_author_organization: 'Sanford Burnham Prebys Medical Discovery Institute'
    - add_author_degree: Bachelor
      add_author_first_name: 'Yan Yuen'
      add_author_last_name: Lo
      add_author_middle: ''
      add_author_organization: 'Sanford Burnham Prebys Medical Discovery Institute'
    - add_author_degree: PhD
      add_author_first_name: Jon
      add_author_last_name: Larson
      add_author_middle: ''
      add_author_organization: 'Sanford Burnham Prebys Medical Discovery Institute'
    - add_author_degree: MD
      add_author_first_name: Sunita
      add_author_last_name: Sridhar
      add_author_middle: ''
      add_author_organization: 'Rady Children’s Hospital'
    - add_author_degree: PhD
      add_author_first_name: Owen
      add_author_last_name: Chapman
      add_author_middle: ''
      add_author_organization: 'Nagoya City University Graduate School of Medicine'
    - add_author_degree: PhD
      add_author_first_name: Lukas
      add_author_last_name: Chavez
      add_author_middle: ''
      add_author_organization: 'Sanford Burnham Prebys Medical Discovery Institute'
  abstract: "Extrachromosomal DNA (ecDNA) is a key driver of intratumoral heterogeneity and has been linked to therapeutic resistance and poor patient outcomes. However, technical limitations in identifying, isolating, and analyzing ecDNA at the single-cell level have hindered our understanding of its role in tumor development and treatment response. We have previously developed a single-cell multiome (RNA + ATAC) sequencing approach that enables the simultaneous analyses of ecDNA and its gene expression profiles. Initial application of this method in a medulloblastoma tumor of the sonic hedgehog subgroup revealed distinct transcriptional signatures in ecDNA-positive compared to ecDNA-negative and non-malignant cells. Building on these findings, we performed single-cell multiome sequencing on an additional cohort of medulloblastoma specimens harboring ecDNA amplifications, obtained from Rady Children's Hospital and the Children's Brain Tumor Network (CBTN). Initial analyses revealed distinct functional characteristics between ecDNA-positive and ecDNA-negative tumor cells. For example, ecDNA-positive tumor cells show up-regulation of DNA replication, recombination, and damage repair pathways, while ecDNA-negative cells demonstrated increased expression of synaptic activity, cell signaling, and morphogenesis pathways. Our ongoing analysis focuses on further defining the transcriptional programs that distinguish ecDNA-positive from ecDNA-negative tumor cells, ultimately informing future functional genetic and pharmacological studies targeting transcriptional dependencies in ecDNA-driven medulloblastoma tumors."
  abstract_title_: 'Single-Cell Multiome Sequencing Reveals Distinct Transcriptional Programs Associated with ecDNA Amplifications in Medulloblastoma'
  email_address_: ahui@sbpdiscovery.org
  institution_: 'Sanford Burnham Prebys Medical Discovery Institute'
  presenting_author_: 'Hui Hui'