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On the frequency of genome rearrangement events in cancer karyotypes

Chromosomal instability is a hallmark of cancer. The results of this instability can be observed in the karyotypes of many cancerous genomes, which often contain a variety of aberrations. In this study we introduce a new approach for analyzing rearrangement events in carcinogenesis. This approach builds on a new effective heuristic for computing a short sequence of rearrangement events that may have led to a given karyotype. We applied this heuristic on over 40,000 karyotypes reported in the scientific literature. Our analysis implies that these karyotypes have evolved predominantly via four principal event types: chromosomes gains and losses, reciprocal translocations, and terminal deletions. We used the frequencies of the reconstructed rearrangement events to measure similarity between karyotypes. Using clustering techniques, we demonstrate that in many cases, rearrangement event frequencies are a meaningful criterion for distinguishing between karyotypes of distinct tumor classes. Further investigations of this kind can provide insight on the scenarios by which particular cancer types have evolved.