The elusive evidence for chromothripsis.
Bottom Line: Lastly, we provide an algorithm to find a sequence of progressive rearrangements that explains all observed breakpoints from a proposed chromothripsis chromosome.Thus, the proposed signature cannot be considered a sufficient proof for this extraordinary hypothesis.Great caution should be exercised when labeling complex rearrangements as chromothripsis from genome hybridization and sequencing experiments.
Affiliation: Bioinformatics and Systems Biology Program, University of California, San Diego, CA, USA.Show MeSH
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Mentions: Finally, we altered the way the simulation chooses breakpoints to introduce into the chromosome. In the original simulation, breakpoints were chosen uniformly randomly without replacement, so each remaining breakpoint had an equal chance of being introduced at each step. This may not correspond to biological reality as there may be some preference for particular kinds of rearrangements. Specifically, a preference for inversions over other rearrangement types could lead to chromosomes with many breakpoints but few copy number states. To test this, we changed the simulation so that inversions were twice as likely to be chosen at each step compared to deletions or duplications. The results are in Figure 4a and b, using PES and microarray breakpoint counting, respectively. These results have many simulated chromosomes bearing the footprint of chromothripsis. The large fraction of chromosomes with many breakpoints and few copy number states (Table 2) indicates that some chromosomes that appear to have undergone chromothripsis could also have been produced by progressive rearrangement that favors inversions.
Affiliation: Bioinformatics and Systems Biology Program, University of California, San Diego, CA, USA.