Fig. 3: Chromothripsis is a major event for the formation of ecDNAs.
a Copy number plots for ecDNA carrying the GLI2 oncogene (whole-genome view and zoom on chromosome 2) generated by a CT event detected in the MB243-Nuclei sample (shown in panels a–f). b Structure of the ecDNA carrying GLI2 confirmed by bulk WGS assembly (derived using AmpliconArchitect; “Methods”). Blue rectangles show genomic segments. Arrows denote the orientation of a segment from lower to higher coordinates. c scDNA-seq of tumour nuclei shows high copy-numbers of the segments included in the ecDNA (the number of copies of the GLI2 locus located on the ecDNAs is used as a proxy for the number of ecDNA copies). Most tumour cells carry 10 to 40 copies of the ecDNA, with more than 100 copies per cell in extreme cases. Scale bar, 5 µm. d Relationship between CT on chromosome 2 (using the number of CNV segments on Chr. 2 per cell as a proxy for chromothripsis) and the number of copies of ecDNAs. Subsets of tumour cells carry both the CT chromosome and ecDNAs while other cells keep the ecDNA but may have lost the CT chromosome. e Number of copies of ecDNAs per clone (using the number of copies of GLI2 as a proxy). Significance is displayed from Bonferroni adjusted p values. f Tumour cells with ecDNAs including GLI2 show a high expression of this oncogene (left, sample MB243-Nuclei; right, GLI2 expression in sample LFS-MBP-Nuclei for comparison with a sample without ecDNA including GLI2). g FISH validation of ecDNAs carrying GLI2 likely generated by CT on chromosome 2 (BT084-PDX sample). In addition to the GLI2 probe (red), we used a multicolour probe for chromosome 2. Scale bar, 10 µm. h Sonic Hedgehog medulloblastomas with ecDNAs have a significantly higher CT prevalence (n = 46; two-sided Fisher exact test). i CT is significantly linked with the presence of ecDNAs across nine tumour types (colon cancer, haematological malignancies, prostate cancer, breast cancer, ovarian cancer, melanoma, renal cancer, lung cancer and glioblastoma, two-sided pearson correlation test shown, reanalysis from3,77). R, Pearson correlation coefficient. Source data are provided as a Source Data file.
