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| Status |
Public on Sep 15, 2023 |
| Title |
Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Circular extrachromosomal DNA (ecDNA) in patient tumor genomes is an important driver of oncogenic gene expression, evolution of drug resistance, and poor patient outcomes. Applying computational methods for detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma (MB) tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA+ MB were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. Individual tumors harbor multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging, and CRISPR inhibition experiments in MB 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 a subset of highly aggressive MB tumors, and suggests copy number heterogeneity and enhancer rewiring as clinically relevant features of ecDNA in MB.
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| Overall design |
Bulk ATAC-seq of frozen primary medulloblastomas (MB***). ATAC-seq of frozen patient-derived xenograft (PDX) mouse model (RCMB56). ATAC-seq of cell line D458.
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| Contributor(s) |
Chapman OS, Chavez L, Mesirov JP, Fraenkel E |
| Citation(s) |
37945900 |
| Submission date |
Aug 14, 2023 |
| Last update date |
Dec 14, 2023 |
| Contact name |
Lukas Chavez |
| E-mail(s) |
lchavez@sbpdiscovery.org
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| Phone |
(858)952-3775
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| Organization name |
Sanford Burnham Prebys Medical Discovery Institute
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| Department |
Cancer Genome and Epigenetics Program, NCI-Designated Cancer Center
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| Street address |
10901 North Torrey Pines Road
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (27)
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| GSM7710214 |
MB099, G4, ATAC |
| GSM7710215 |
MB102, SHHa, ATAC |
| GSM7710216 |
MB104, SHHa, ATAC |
| GSM7710217 |
MB106, G3a, ATAC |
| GSM7710218 |
MB136, SHHb, ATAC |
| GSM7710219 |
MB164, G3b, ATAC |
| GSM7710220 |
MB174, G4, ATAC |
| GSM7710221 |
MB199, G4, ATAC |
| GSM7710222 |
MB227, G4, ATAC |
| GSM7710223 |
MB234, SHHa, ATAC |
| GSM7710224 |
MB244, SHHa, ATAC |
| GSM7710225 |
MB247, G3a, ATAC |
| GSM7710226 |
MB248, G3a, ATAC |
| GSM7710227 |
MB264, G4, ATAC |
| GSM7710228 |
MB268, SHHa, ATAC |
| GSM7710229 |
MB274, SHHa, ATAC |
| GSM7710230 |
MB275, SHHa, ATAC |
| GSM7710231 |
MB277, G3b, ATAC |
| GSM7710232 |
MB278, G3b, ATAC |
| GSM7710233 |
MB281, G4, ATAC |
| GSM7710234 |
MB282, G4, ATAC |
| GSM7710235 |
MB288, G3b, ATAC |
| GSM7710236 |
D458, G3, ATAC |
| GSM7710237 |
RCMB56-ht, SHH, ATAC |
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| This SubSeries is part of SuperSeries: |
| GSE240985 |
Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas |
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| Relations |
| BioProject |
PRJNA1005316 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE240830_RAW.tar |
6.1 Gb |
(http)(custom) |
TAR (of BW, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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