Figure 1.

Characteristics of Chromothripsis, Chromoplexy, and Chromoanasynthesis-Derived SVs

(A) A chromosome in a micronucleus can undergo massive DNA damage and result in multiple double-strand breaks (DSBs, depicted with dashed black lines). When the micronucleus is re-incorporated into the nucleus during mitosis, the DSBs undergo repair through NHEJ, where chromosome segments are randomly stitched back together, lost, or become double minutes. Functionally relevant segments could become double minutes and undergo amplification, as has been observed in MYC and other oncogene-containing segments in various cancer cases.^{19, 29, 30}

(B) In chromoplexy, different DSBs can be repaired with or without DNA loss at the breakpoints and be arranged into various derivative configurations, as shown here by the rearrangements of example chromosomes A, B, and C.

(C) In chromoanasynthesis, a normal chromosome can undergo DNA segment re-synthesis (dashed lines to show template switches and solid arrows to show replication) mediated by replication processes such as FoSTeS and MMBIR. These mechanisms lead to templated insertions that exhibit higher copy-number and may be arranged in different orientations (depicted in purple and orange with white arrows signifying inverted sequence orientation). Notice the chromoanasynthesis chromosome has a copy-number profile exhibiting intercalating duplication-normal-duplication (dup-nml-dup) copy-number states, as seen in previous studies.²¹