Figure 2: Chromatin organization and its disruption by rearrangements in cancer.

A) The three-dimensional organization of DNA. Chromatin fibers can form regions of close interactions such as topologically associated domains (TADs). At the largest scale, chromatin is organized as a fractal globule, in which the likelihood that two sequences within a chromosome will be adjacent in three-dimensional space is proportional to the number of bases that separate them. B) TADs are highly interconnected DNA loops, as indicated by dense triangles in Hi-C maps, where higher interaction frequencies are represented by deeper red. Their boundaries are often defined by CTCF and cohesin binding, and genetic elements that regulate transcription (e.g. promoters, enhancers, and silencers) typically act upon genes within their TAD. C) Effects of SVs on TAD structure and characteristic resulting interaction maps. (top) Situation before the SV with two TADs separated by a boundary element. The ectopic contacts resulting from deletion (left), duplication (middle), and inversion (right) are shown in blue. As apparent in the interaction maps, all three can cause genes to interact with regulatory elements in the neighboring TAD. The reference genome projections (bottom) show characteristic interaction maps for each SV type, which enables their interpretation in Hi-C analysis. Figure panels modified from Spielmann M, Lupiáñez DG, Mundlos S. Nat Rev Genet. 2018.

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.