Fig. 5: 3D genome folding differentiates relapse from primary GBM samples.
a Circos plots of SVs and CNVs in G402 and G402R identified by hicbreakfinder (top) or EagleC (bottom). Outer tracks: chromosomes; inner tracks: gain (red: >2 copies) or loss of genomic segments (blue: <2 copies); lines: translocations (purple), inversions (gray), deletions (light blue) or duplications (red). Aligned below the Circos plots are the top GBM-associated genes (gda>0.01) that are common to both lines or specific to each, and linked to a particular SV type (color-coded). **: The MIR31-associated translocation in the relapse line is different to the primary one. b Venn diagrams showing shared and unique SVs or neoloop-associated genes in primary and relapse Hi-C data identified by hicbreakfinder (top) or EagleC (bottom). c GO terms associated with differentially-expressed genes in primary versus relapse G402. P-values calculated using two-sided Fisher’s exact tests without multiple comparison adjustment. d Percent (mean ± SEM) of differentially-expressed genes explained from n = 3 primary/relapse pairs by A/B-compartment, loop or enhancer changes in all GSC pairs. *: P = 0.0145, unpaired two-sided Student’s t-test. Source data for this panel are provided as a Source Data file. e As in panel d, but for differentially-expressed genes linked to E-P loops gained (orange), lost (green) or not changed upon relapse (gray). *: P = 0.0331, unpaired two-sided Student’s t-test. Source data for this panel are provided as a Source Data file. f Left: APA plot for neoloops specific to primary or relapse GSC pairs. Right: Box plots (bands show the mean, each box extends between 1st and 3rd quartile, and whiskers extend 1.5x the interquartile range) showing changes in the expression of genes associated with loops gained (red) or lost (blue), having increased (orange) or decreased H3K27ac (light blue), or not changing in relapse (white). *: P (from left to right) = 1.60e-05, 2.09e-01, 3.26e-12 and 4.26e-12, two-sided Wilcoxon-Mann-Whitney test. Source data for this panel are provided as a Source Data file. g Hi-C contact maps around a 17.6-Mbp deletion on chr9 specific to G402R shown aligned to overlaid RNA-seq and H3K27ac tracks from primary (black) and relapse samples (yellow). G402-specific neoloops are indicated (blue circles).
