Figure 4: Effects on fitness that shape SVs in cancer.

A) Five mechanisms by which SVs can increase expression of nearby oncogenes. (1) Enhancer juxtaposition. A lineage-specific enhancer, which promotes tissue-specific expression, is juxtaposed with an oncogene. (2) CRE-gene fusions. Additional cis-regulatory elements such as promoters are juxtaposed with the oncogene. (3) Enhancer de novo looping. The SV generates new long-range loops involving lineage-specific enhancers. (4) Enhancer amplification. A low-activity enhancer is amplified, multiplying its effects on expression of oncogenes within its TAD. (5) Extrachromosomal amplification. Combinations of the three prior mechanisms are active in extrachromosomal amplicons. These often contain enhancers hijacked from distant sites, and their circular topology circumvents insulators, allowing enhancers from the whole amplicon to interact with contained oncogenes. B) Positions of oncogenic SVs and their mechanisms of activation, indicated by the colored circles below affected oncogenes.

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.