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

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

PROVIDER: PRJNA1005313 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25635526_1.fastq.gz	Fastqsanger.gz
	SRR25635526_2.fastq.gz	Fastqsanger.gz
	SRR25635527_1.fastq.gz	Fastqsanger.gz
	SRR25635527_2.fastq.gz	Fastqsanger.gz
	SRR25635528_1.fastq.gz	Fastqsanger.gz

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

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

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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 [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 [scRNA+ATAC-seq]

Project description: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 [ATAC-seq]

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Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [eccDNA-seq]

Project description:Extrachromosomal circular DNA (eccDNA) is double-stranded circular DNA that is derived from but independent of chromosomal DNA. Owing to its nonchromosomal inheritance, eccDNA facilitates the amplification of oncogenes and expedites the process of genome evolution in tumor. However, the role of eccDNA in RB remains enigmatic. We combined Circle-Seq and RNA-Seq to identified crucial extrachromosomal circular oncogene amplicons. Herein, we revealed that extrachromosomal circular SUZ12 amplicon regulates H3K27me3 modification during the oncogenic progression of retinoblastoma. Conclusively, our study initially delineated an integrated picture of the eccDNA landscape in retinoblastoma and unveiled a novel SUZ12-containing eccDNA/H3K27me3 oncogenic mechanism where eccDNA dictates retinoblastoma progression through regulating transcription levels of linear DNA.

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Effects of nucleases on cell-free extrachromosomal circular DNA

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