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. 2023 May 17;618(7967):1024–1032. doi: 10.1038/s41586-023-06057-w

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 5 — a. ‘Dual-LOH’ pattern of the bridge arms in the tumors with TB amplification. Both bridge arms in each case show substantial loss of heterozygosity (LOH). Notably, the bridge arm segments proximal to the TB amplification (the inter-centromeric segment on the bridge) often show complex copy-number pattern with segmental loss (first panel; in BR014) or gain (second panel; in TCGA-EW-A1J5) by one copy. This is likely due to the unequal breakpoints between the sister dicentrics. Depending on the location of the break, some segments can be duplicated (exhibiting one-copy gain) or lost (one-copy loss) in a daughter cell after the bridge resolution. b. Copy number outcome after the translocation forming a single dicentric chromosome, chromosome bridge, and its resolution. The two daughter cells will inherit one broken arm after the bridge breakage, leading to their ‘single-LOH’ copy-number pattern. c. Three different scenarios of mitotic spindle attachments in the setting of replicated dicentric sisters (initial translocation in G1). If the microtubules are attached in cis, normal mitosis will be secured (upper panel). If in trans, chromosome bridge will be formed by two ‘flipped’ dicentrics in anti-parallel orientation and the resultant copy number profile matches with the dual-LOH pattern frequently observed in breast cancer cases with TB amplifications (middle panel). If the microtubules from one pole are attached to the same centromeres (syntelic attachment), each daughter cell will have LOH affecting one arm of a chromosome and whole length of another chromosome (lower panel). d. Four different copy number outcomes depending on the timing and orientation of the translocation. We expect post-replication inter-chromosomal translocation to be less frequent due to the active homologous recombination in the S/G2 cells. e. Copy-number difference between the two non-bridge arms in the 58 TB amplification events where the two non-bridge arms are globally amplified more than three copies. 36 (62%) out of 58 events showed a copy number difference of less than 2. f. A case indicating possible repair by mutual ligation between the non-bridge arms (8q and 16p) after TB amplification. The two non-bridge arms (8q and 16p) are connected to each other by multiple translocations at the copy-number boundaries. A whole-genome duplication took place after the translocations between non-bridge arms and led to the coordinated copy-number gain.