Human genomes are continuously subjected to mutations, which can drive
genetic diseases and
cancer. An intriguing recent finding has been the discovery of
chromothripsis, a spectacular and complex form of chromosome rearrangement that can occur in the genomes of
cancer cells and patients with congenital diseases.
Chromothripsis has been described in a large array of human
cancers and various types of
chromothripsis have appeared, which differ in complexity and genomic hallmarks. From the combined genomic data a consensus hypothesis has been inferred, involving aberrant DNA replication and
chromosome shattering as the underlying processes explaining
chromothripsis. In addition, recent work has established several cellular models that recapitulate
chromothripsis under defined experimental conditions. One of these models indicates that
chromothripsis can originate from DNA damage in micronuclei, providing an elegant explanation for the restriction of chromothriptic rearrangements to a single chromosome. Alternatively,
chromothripsis can be caused by telomere crisis, a process that involves formation of dicentric chromosomes and
chromatin bridges. Here, we summarize the genomic features of
chromothripsis and we discuss experimental approaches that allow dissection of the
chromothripsis process.