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The Genomic Characteristics and Origin of Chromothripsis.
In 2011 a phenomenon involving complex chromosomal rearrangements was discovered in cancer genomes. This phenomenon has been termed chromothripsis, on the basis of its chromosomal hallmarks, which point to an underlying process involving chromosome (chromo) shattering (thripsis). The prevailing hypothesis of cancer genome evolution as a gradual process of mutation and selection was challenged by the discovery of chromothripsis, because its patterns of chromosome rearrangement rather indicated an one-off catastrophic burst of genome rearrangement. The initial discovery of chromothripsis has led to many more examples of chromothripsis both in cancer genomes as well as in patients with congenital diseases and in the genomes of healthy individuals. Since then, a burning topic has been the study of the molecular mechanism that leads to chromothripsis. Cumulating evidence has shown that chromothripsis may result from lagging chromosomes encapsulated in micronuclei, as well as from telomere fusions followed by chromosome bridge formation. In this chapter, we will outline the genomic characteristics of chromothripsis, and we present genomic methodologies that enable the detection of chromothripsis. Furthermore, we will give an overview of recent insights into the mechanisms underlying chromothripsis.
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