title: Open adjacencies and k-breaks: detecting simultaneous rearrangements in cancer genomes.
abstract: BACKGROUND
  The evolution of a cancer genome has traditionally been described as a sequential accumulation of mutations - including chromosomal rearrangements - over a period of time. Recent research suggests, however, that numerous rearrangements may be acquired simultaneously during a single cataclysmic event, leading to the proposal of new mechanisms of rearrangement such as chromothripsis and chromoplexy.
  
  
  RESULTS
  We introduce two measures, open adjacency rate (OAR) and copy-number asymmetry enrichment (CAE), that assess the prevalence of simultaneously formed breakpoints, or k-breaks with k >2, compared to the sequential accumulation of standard rearrangements, or 2-breaks. We apply the OAR and the CAE to genome sequencing data from 121 cancer genomes from two different studies.
  
  
  CONCLUSIONS
  We find that the OAR and CAE correlate well with previous analyses of chromothripsis/chromoplexy but make differing predictions on a small subset of genomes. These results lend support to the existence of simultaneous rearrangements, but also demonstrate the difficulty of characterizing such rearrangements using different criterion.
authors.forename: Caleb
authors.initials: C
authors.lastname: Weinreb
authors.forename: Layla
authors.initials: L
authors.lastname: Oesper
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Raphael
mesh_terms: D000465:Algorithms; D000818:Animals; D056905:Chromosome Breakpoints; D016678:Genome; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D014178:Translocation, Genetic