Paul S. Mischel
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View article: Enhancer activation from transposable elements in extrachromosomal DNA
Enhancer activation from transposable elements in extrachromosomal DNA Open
View article: Genetic elements promote retention of extrachromosomal DNA in cancer cells
Genetic elements promote retention of extrachromosomal DNA in cancer cells Open
Extrachromosomal DNA (ecDNA) is a prevalent and devastating form of oncogene amplification in cancer 1,2 . Circular megabase-sized ecDNAs lack centromeres and segregate stochastically during cell division 3–6 yet persist over many generati…
View article: Supplementary Figures from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Supplementary Figures from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma Open
Supplementary Figures 1 to 34, detailing additional analyses.
View article: Figure 5 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Figure 5 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma Open
Selection dynamics of EGFR SVs on ecDNA. A, A subclonal EGFRvIII variant on ecDNA in the tumor of patient A23. B, Variant heteroplasmy in the core region of all samples across the GB-UK and PCAWG cohorts, which …
View article: Figure 3 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Figure 3 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma Open
SPECIES spatial modeling of ecDNA evolution. A and B, DNA FISH staining of two representative GBM samples from the GB-UK cohort, revealing (A) EGFR- and (B) PDGFRA-ecDNA. EGFR-ecDNA seem to …
View article: Data from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Data from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma Open
Oncogenes amplified on extrachromosomal DNA (ecDNA) contribute to treatment resistance and poor survival across cancers. Currently, the spatiotemporal evolution of ecDNA remains poorly understood. In this study, we integrate computational …
View article: Figure 4 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Figure 4 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma Open
ecDNA accumulation in genetically engineered in vivo and ex vivo murine models. A, Neural stem cells were propagated within the SVZ of genetically engineered mice for 4 months. B,Myc-ecDNAs were in…
View article: Supplementary Methods from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Supplementary Methods from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma Open
Supplementary Methods, providing details about methodology used throughout the study.
View article: Figure 6 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Figure 6 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma Open
Simulating multi-ecDNA dynamics in vivo.A, DNA FISH and nascent RNAscope images from the tumor of patient A5, showing the coexistence of both EGFR-ecDNA and PDGFRA-ecDNA. B, Circular structures of three d…
View article: Figure 1 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Figure 1 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma Open
Workflow of the study analysis. A, A total of 94 IDHwt GBMs were analyzed (35 from the PCAWG cohort and 59 from the GB-UK cohort). B, The core region of all patient tumors was analyzed using WGS, and GB-UK patient tumo…
View article: Figure 2 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Figure 2 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma Open
Diversity and high copy numbers of ecDNA in IDHwt GBMs. A, Focal copy-number amplifications across the GB-UK and PCAWG cohorts, categorized by amplicon type [ecDNA, breakage–fusion–bridge (BFB) cycle, linear]. Only tumors con…
View article: Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma
Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma Open
Oncogenes amplified on extrachromosomal DNA (ecDNA) contribute to treatment resistance and poor survival across cancers. Currently, the spatiotemporal evolution of ecDNA remains poorly understood. In this study, we integrate computational …
View article: Applying multilevel selection to understand cancer evolution and progression
Applying multilevel selection to understand cancer evolution and progression Open
Natural selection occurs at multiple levels of organization in cancer. At an organismal level, natural selection has led to the evolution of diverse tumor suppression mechanisms, while at a cellular level, it favors traits that promote cel…
View article: Extrachromosomal DNA: shaping the evolutionary dynamics of cancer
Extrachromosomal DNA: shaping the evolutionary dynamics of cancer Open
Cancers are complex, diverse, and elusive, with extrachromosomal DNA (ecDNA) recently emerging as a crucial player in driving the evolution of about 20% of all tumors. In this review we discuss open questions concerning the evolutionary ro…
View article: Oxidative stress is a shared characteristic of ME/CFS and Long COVID.
Oxidative stress is a shared characteristic of ME/CFS and Long COVID. Open
Over 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition marked by fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME…
View article: Accurate Prediction of ecDNA in Interphase Cancer Cells using Deep Neural Networks
Accurate Prediction of ecDNA in Interphase Cancer Cells using Deep Neural Networks Open
Oncogene amplification is a key driver of cancer pathogenesis and is often mediated by extrachromosomal DNA (ecDNA). EcDNA amplifications are associated with increased pathogenicity of cancer and poorer outcomes for patients. EcDNA can be …
View article: Data from A Guide to Extrachromosomal DNA: Cancer’s Dynamic Circular Genome
Data from A Guide to Extrachromosomal DNA: Cancer’s Dynamic Circular Genome Open
Focal amplifications of oncogenes are important cancer drivers. They can occur on chromosomes or in the context of circular extrachromosomal DNA (ecDNA). Many key features of ecDNAs were described in the 1960s to 1980s, including their “un…
View article: Figure S1 from A Guide to Extrachromosomal DNA: Cancer’s Dynamic Circular Genome
Figure S1 from A Guide to Extrachromosomal DNA: Cancer’s Dynamic Circular Genome Open
Summary of key differences between ecDNA and eccDNA
View article: Data from Spatial–Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment
Data from Spatial–Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment Open
Extrachromosomal DNA (ecDNA) presents a promising target for cancer therapy; however, its spatial–temporal diversity and influence on tumor evolution and the immune microenvironment remain largely unclear. We apply computational methods to…
View article: Supplementary Figures 1-12 from Spatial–Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment
Supplementary Figures 1-12 from Spatial–Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment Open
Supplementary Figure 1. Prevalence of ecDNA in human cancers. Supplementary Figure 2. Characteristics of ecDNA. Supplementary Figure 3. ecDNA drives massive oncogene expression in UC. Supplementary Figure 4. ecDNA can arise in flat urothel…
View article: Supplementary Tables 1-24 from Spatial–Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment
Supplementary Tables 1-24 from Spatial–Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment Open
Table_S1. Study cohort. Table_S2. The sample composition of each dataset. Table_S3. Patient information. Table_S4. Whole genome sequencing (WGS) datasets. 1,411 UC whole genomes. Table_S5. Whole exome sequencing (WES) datasets. Table_S6. R…
View article: A Guide to Extrachromosomal DNA: Cancer’s Dynamic Circular Genome
A Guide to Extrachromosomal DNA: Cancer’s Dynamic Circular Genome Open
Focal amplifications of oncogenes are important cancer drivers. They can occur on chromosomes or in the context of circular extrachromosomal DNA (ecDNA). Many key features of ecDNAs were described in the 1960s to 1980s, including their “un…
View article: Unified molecular approach for spatial epigenome, transcriptome, and cell lineages
Unified molecular approach for spatial epigenome, transcriptome, and cell lineages Open
Spatial epigenomics and multiomics can provide fine-grained insights into cellular states but their widespread adoption is limited by the requirement for bespoke slides and capture chemistries for each data modality. Here, we present SPati…
View article: Oncogene Silencing via ecDNA Micronucleation
Oncogene Silencing via ecDNA Micronucleation Open
Extrachromosomal DNA (ecDNA) is a common source of oncogene amplification across many types of cancer. The non-Mendelian inheritance of ecDNA contributes to heterogeneous tumour genomes that rapidly evolve to resist treatment. Here, using …
View article: EcDNA-borne PVT1 fusion stabilizes oncogenic mRNAs
EcDNA-borne PVT1 fusion stabilizes oncogenic mRNAs Open
Summary Extrachromosomal DNA (ecDNA) amplifications are prevalent drivers of human cancers. We show that ecDNAs exhibit elevated structural variants leading to gene fusions that produce oncogene fusion transcripts. The long noncoding RNA (…
View article: Inhibition of human-HPV hybrid ecDNA enhancers reduces oncogene expression and tumor growth in oropharyngeal cancer
Inhibition of human-HPV hybrid ecDNA enhancers reduces oncogene expression and tumor growth in oropharyngeal cancer Open
Extrachromosomal circular DNA (ecDNA) has been found in most types of human cancers, and ecDNA incorporating viral genomes has recently been described, specifically in human papillomavirus (HPV)-mediated oropharyngeal cancer (OPC). However…
View article: Spatial–Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment
Spatial–Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and the Tumor Immune Microenvironment Open
Extrachromosomal DNA (ecDNA) presents a promising target for cancer therapy; however, its spatial–temporal diversity and influence on tumor evolution and the immune microenvironment remain largely unclear. We apply computational methods to…
View article: Breakage fusion bridge cycles drive high oncogene number with moderate intratumoural heterogeneity
Breakage fusion bridge cycles drive high oncogene number with moderate intratumoural heterogeneity Open
Oncogene amplification is a key driver of cancer pathogenesis. Both breakage fusion bridge (BFB) cycles and extrachromosomal DNA (ecDNA) can lead to high oncogene copy numbers, but the impact of BFB amplifications on intratumoral heterogen…
View article: Supplementary Data Set 1 from Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair
Supplementary Data Set 1 from Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair Open
sgRNA, primer, and probe sequences.
View article: Data from Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair
Data from Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair Open
Oncogene amplification on extrachromosomal DNA (ecDNA) is a pervasive driver event in cancer, yet our understanding of how ecDNA forms is limited. In this study, we couple a CRISPR-based method for ecDNA induction with extensive characteri…