Fig. 5: Enhancer rewiring in medulloblastoma ecDNA affects cell proliferation.
From: Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma
a, Confocal FISH microscopy of MYC and OTX2 on a D458 metaphase cell. Representative image of six metaphase cells. Scale bar, 10 μm. b, Gene transcription of all protein-coding genes in D458 and D283 from publicly available data in DepMap62. Medulloblastoma Group 3 oncogenes MYC and OTX2 are highlighted. TPM, transcripts per million. c, Chromatin accessibility and interactions mapped onto the D458 amplicon. Tracks from outer to inner: genome sequence, internally duplicated sequences, chromatin accessibility, chromatin interactions. d, FISH in a metaphase spread of a D283 nucleus shows homogeneously staining region (HSR) chromosomal MYC amplification. Representative image of 11 metaphase cells. Scale bar, 10 μm. e, Pooled CRISPRi screen in medulloblastoma cell lines D458 and D283 targeting all accessible loci on the D458 ecDNA. Tracks from top to bottom: D458 ecDNA-amplified loci; D283 HSR-amplified loci; genes; D458 chromatin accessibility; CRISPRi essentiality scores for D458 and D283 generated by CRISPR-SURF63. Vertical highlighted bars indicate accessible loci that are significantly depleted at T21 relative to T0 and are colored by cell line specificity. Gray: essential in D458 and D283 with no significant difference; green: essential in D458 relative to D283; yellow: essential in D283 relative to D458. Significance determined by MAGeCK MLE permutation test adjusted for false discovery rate52 (q < 0.05).
