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[Preprint]. 2023 Dec 13:2023.12.12.571349. [Version 1] doi: 10.1101/2023.12.12.571349

Figure 4:

Figure 4:

A) Top: The structure of the MYC-amplified ecDNA from the COLO320DM cell line. Blue arrows indicate genomic segments from chr 8 amplified on the ecDNA; black dashed lines indicate SV breakpoints directly connecting two remote genomic segments; gray dashed lines indicate templated insertions of segments involving other chromosomes. Middle: Normalized HiChIP contact map of COLO320DM at the ecDNA locus. Blue spots indicate significant chromatin interactions identified by NeoLoopFinder; while black spots indicate “neoloops” proximal to SV breakpoints and likely to be formed due to the genomic segments coming together in the cell line. Bottom: Normalized HiChIP contact map of GM12878 at the identical chr8 locus. Blue spots indicate significant chromatin interactions.

B) Top: The inferred structure of the BFB-like focal amplification from the COLO320DM cell line. Middle: Normalized HiChIP contact map of COLO320DM at the BFB locus. Blue spots indicate significant chromatin interactions identified by NeoLoopFinder. Bottom: Normalized HiChIP contact map of GM12878 at the identical chr1 locus. Blue spots indicate significant chromatin interactions.

C) Distribution of HiChIP interaction frequencies in ecDNA and BFB-driven amplifications. For a specific genomic distance d (x-axis), the dot represents the fraction, among all pairs of genomic windows separated by d, of pairs with significant HiChIP interactions.

D) Differences in immune cell subtype compositions in BFB(+) cancers (n=76) versus ecDNA(+) cancers (n=297). (* indicates p<0.05; ** ⇒ p<0.01; *** ⇒ p<0.001).

E) Targeted Therapy Resistance of the HCC827 Cell Line continuing EGFR amplified within a BFB event. The top panel shows the BFB architecture in the HCC827 naive cell line along with metaphase FISH images. Resistance formation to Erlotinib (ER) maintains the BFB amplicon structure, but the bulk copy number is highly reduced. The copy number and the proportion of cells carrying the BFB signal are restored after drug removal (ERDR). No changes were observed in the BFB amplification in Lapatinib drug resistant (LR) line.