Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Functional enhancers shape extrachromosomal oncogene amplifications

ABSTRACT: Functional enhancers shape extrachromosomal oncogene amplifications

PROVIDER: PRJNA579579 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Engineered extrachromosomal oncogene amplifications promote tumorigenesis

Project description:Engineered extrachromosomal oncogene amplifications promote tumorigenesis

| PRJNA1100533 | ENA

Functional Enhancers Shape Extrachromosomal Oncogene Amplifications.

Project description:Non-coding regions amplified beyond oncogene borders have largely been ignored. Using a computational approach, we find signatures of significant co-amplification of non-coding DNA beyond the boundaries of amplified oncogenes across five cancer types. In glioblastoma, EGFR is preferentially co-amplified with its two endogenous enhancer elements active in the cell type of origin. These regulatory elements, their contacts, and their contribution to cell fitness are preserved on high-level circular extrachromosomal DNA amplifications. Interrogating the locus with a CRISPR interference screening approach reveals a diversity of additional elements that impact cell fitness. The pattern of fitness dependencies mirrors the rearrangement of regulatory elements and accompanying rewiring of the chromatin topology on the extrachromosomal amplicon. Our studies indicate that oncogene amplifications are shaped by regulatory dependencies in the non-coding genome.

| S-EPMC7241652 | biostudies-literature

Engineered extrachromosomal oncogene amplifications promote tumorigenesis (RNA-Seq)

Project description:Engineered extrachromosomal oncogene amplifications promote tumorigenesis (RNA-Seq)

| PRJNA1100544 | ENA

Functional enhancers shape extrachromosomal oncogene amplifications

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-11-25 | GSE139417 | GEO

Engineered extrachromosomal oncogene amplifications promote tumorigenesis [shallow whole genome sequencing and ATACseq]

Project description:Engineered extrachromosomal oncogene amplifications promote tumorigenesis [shallow whole genome sequencing and ATACseq]

| PRJNA1101531 | ENA

Engineered extrachromosomal oncogene amplifications promote tumorigenesis (RNA-Seq)

Project description:Focal gene amplifications are among the most common cancer-associated mutations, but their evolution and contribution to tumorigenesis have proven challenging to recapitulate in primary cells and model organisms. Here we describe a general strategy to engineer large (>1 Mbp) focal amplifications mediated by extrachromosomal circular DNAs (ecDNAs) in a spatiotemporally controlled manner in cells and in genetically engineered mice. By coupling ecDNA formation with expression of selectable markers, we track the dynamics of ecDNA-containing cells under physiological conditions and in the presence of specific selective pressures. We also apply this approach to generate mice harboring Cre-inducible Myc- and Mdm2-containing ecDNAs analogous to those occurring in human cancers. We show that the engineered ecDNAs spontaneously accumulate in primary cells derived from these animals, promoting their proliferation, immortalization, and transformation. Finally, we demonstrate the ability of Mdm2-containing ecDNAs to promote tumor formation in an autochthonous mouse model of hepatocellular carcinoma.

2024-10-05 | GSE264003 | GEO

Circular extrachromosomal DNA drives massive oncogene expression and chromatin accessibility

Project description:Oncogenes are commonly amplified on extrachromosomal DNA particles (ecDNA) in cancer, but our understanding of the structure of ecDNA and its impact on gene regulation is limited. We integrated ultrastructural imaging, long range-optical mapping, and computational analysis of whole genome sequencing to demonstrate unequivocally that ecDNA is circular. Pan-cancer analyses reveal that the oncogenes encoded on ecDNA are among the most highly expressed genes in the transcriptome of tumours, linking elevated copy with very high levels of transcription. Quantitative assessment of the chromatin state, including ATAC-seq to map the accessible genome and ATAC-see to examine spatial distribution of open chromatin, reveal that while ecDNA is chromatinized, it lacks higher order compaction typical of chromosomes. In fact, ecDNA contains the most accessible DNA in the tumour genome. Using chromosome conformation capture technologies and CRISPR interference, we reveal the differential organization of active chromatin in cancer that is dictated by the circular shape of ecDNA. Lastly, we develop comprehensive maps that provide new insight into how circular ecDNA structure determines oncogene function, bridging ecDNA biology with modern cancer genomics and epigenetics.

2019-12-31 | GSE131956 | GEO

Engineered extrachromosomal oncogene amplifications promote tumorigenesis [shallow whole genome sequencing and ATACseq]

2024-10-05 | GSE264240 | GEO

Integrated analysis of extrachromosomal DNA elements in SCLC [HiChIP]

Project description:Integrated analysis of whole-genome sequencing, long-range optical mapping, single-cell DNA sequencing, and fluorescence in situ hybridization to find extrachromosomal DNA (ecDNA) as the primary source of MYC amplifications and driver fusions in SCLC. ecDNAs bring to proximity enhancer elements and oncogenes through circularization, creating transcription-amplifying units, driving heterogeneity of MYC gene dosage and expression of SCLC lineage-defining transcription factors.

2023-01-24 | GSE206351 | GEO