Massive genomic rearrangement acquired in a single catastrophic event during cancer development.
Bottom Line: Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states.The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ∼25% of bone cancers.We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis.
Affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.Show MeSH
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Mentions: One question that arises is whether the rearrangements are all found on a single parental copy of the chromosome or whether both copies are involved. We therefore performed spectral karyotyping on the three cell lines (Figure 3A and Figure S3). TK10, a hyperdiploid line, carries six copies of chromosome 5. Consistent with the observed copy number profile alternating between states of copy number 4 with LOH and copy number 6 with heterozygosity, the karyotype showed four grossly normal copies of chromosome 5 and two smaller derivative chromosomes. Similarly, in 8505C, two copies of chromosome 9 showed distinctly foreshortened p arms alongside two cytogenetically normal chromosomes. None of the three karyotypes indicated translocations involving the respective derivative chromosomes, confirming the impression from the paired-end sequencing data that the genomic remodeling of these regions was entirely intrachromosomal. Cytogenetic changes were consistently seen across all cells examined.
Affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.