Cancer genomes evolve in a punctuated manner during tumor evolution. Abrupt genome restructuring at key steps in this evolution has been called "genome chaos." To answer whether widespread genome change is truly chaotic, this review (i) summarizes the limited number of cell and molecular systems that execute genome restructuring, (ii) describes the characteristic signatures of DNA changes that result from activity of those systems, and (iii) examines two cases where genome restructuring is determined to a significant degree by cell type or viral infection. The conclusion is that many restructured cancer genomes display sufficiently unchaotic signatures to identify the cellular systems responsible for major oncogenic transitions, thereby identifying possible targets for therapies to inhibit tumor progression to greater aggressiveness.
Keywords: DNA break repair; alternative end-joining (alt-EJ); chromoanasynthesis; chromoplexy; chromothripsis; class switch recombination (CSR); human papillomavirus (HPV); immunoglobulin VDJ joining; retrotransposition; target-primed reverse transcription (TPRT).