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

Abstract Submission for Poster Presentation
-------------------------------------------
Abstract Title:: Single-Cell Multiome Sequencing Reveals Distinct Transcriptional Programs Associated with ecDNA Amplifications in Medulloblastoma
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.

Authors::
1. First Name: Hui
   Last Name: Hui
   Degree(s): Master
   Organization: University of California San Diego
2. First Name: Jessica
   Last Name: Wang
   Degree(s): Bachelor
   Organization: Sanford Burnham Prebys Medical Discovery Institute
3. First Name: Rishaan
   Last Name: Kenkre
   Degree(s): Bachelor
   Organization: Sanford Burnham Prebys Medical Discovery Institute
4. First Name: Yan Yuen
   Last Name: Lo
   Degree(s): Bachelor
   Organization: Sanford Burnham Prebys Medical Discovery Institute
5. First Name: Jon
   Last Name: Larson
   Degree(s): PhD
   Organization: Sanford Burnham Prebys Medical Discovery Institute
6. First Name: Sunita
   Last Name: Sridhar
   Degree(s): MD
   Organization: Rady Children’s Hospital
7. First Name: Owen
   Last Name: Chapman
   Degree(s): PhD
   Organization: Nagoya City University Graduate School of Medicine
8. First Name: Lukas
   Last Name: Chavez
   Degree(s): PhD
   Organization: Sanford Burnham Prebys Medical Discovery Institute

Presenting Author:: Hui Hui
Institution:: Sanford Burnham Prebys Medical Discovery Institute
Email Address:: ahui@sbpdiscovery.org