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Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240985 | GEO | 2023/09/14

REPOSITORIES: GEO

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Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [ATAC-seq]

Project description: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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Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [pooled CRISPRi]

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Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [Hi-C]

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Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [scRNA+ATAC-seq]

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Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas

Project description:Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas

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Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [Hi-C]

Project description:Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [Hi-C]

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Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [ATAC-seq]

Project description:Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [ATAC-seq]

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Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [pooled CRISPRi]

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Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [scRNA+ATAC-seq]

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Deciphering extrachromosomal circular DNA in Arabidopsis.

Project description:Extrachromosomal circular DNA (eccDNA) is independent of the chromosome and exists in many eukaryotes. However, the nature and origin of eccDNA in plants remains unclear. In this study, we sequenced 12 samples from four tissues (leaf, flower, stem and root) with three biological replicates. In total, we found 743 eccDNAs found in at least two samples. Most of eccDNA have inverted repeats ranging from 4 to 12 bp in the boundaries. Interestingly, eccDNA is not only related to transposon activity, but also hosts tRNA genes, suggesting that the eccDNAs may be associated with tRNA abundance which controls protein synthesis under conditions of stress. Our results provide an unprecedented view of eccDNA, which is still naïve in scope.

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