Figure 3: Mechanistic biases of SV formation.

A) Cancer cells accumulate variants that are advantageous (positively selected drivers), or neutral or even deleterious (passengers). Even clones with neutral or deleterious events can expand if they coincide with drivers, or simply due to chance. B) The probability of DSB formation at a genomic locus depends on a combination of its characteristics, including proximity to active transcription (e.g. due to TOP2B-associated DSBs), repeat elements, GC content, and chromatin organization. C) The probability two loci fuse is primarily determined by their 3D distance. While this often correlates with genomic distance, DSBs in flexible regions can fuse to genomically distant loci due to 3D proximities. D) Following a DSB event multiple response factors including PARP1, ATM/ATR, and ALC1 are recruited to modify the surrounding histones. Collectively these changes result in a change of DNA topology towards increased mobility of the break ends.

The figures for this paper were produced by Nature Reviews Cancer graphics artists and are under copyright to Nature Reviews Cancer. The figures can be viewed at : Dubois F, Sidiropoulos N, Weischenfeldt J, Beroukhim R. Structural variations in cancer and the 3D genome. Nature Reviews Cancer. 2022 September;22(9):533–546. PMID: 35764888; DOI: 10.1038/s41568-022-00488-9.