Chromosome Segregation Errors Promote a Diverse Spectrum of Simple and Complex Genomic Rearrangements

Dataset ID Technology Samples
EGAD00001004163 HiSeq X Ten,Illumina HiSeq 2000 22

Dataset Description

Cancer genomes are frequently characterized by numerical and structural karyotypic abnormalities. Here we combined an inducible centromere-specific inactivation approach with selection for a conditionally essential gene, a strategy we term ‘CEN-SELECT’, and show that single-chromosome missegregation during cell division can directly drive a broad spectrum of structural rearrangement types. Cytogenetic profiling revealed that missegregated chromosomes are 120-fold more susceptible to developing seven major categories of structural variants, including translocations, insertions, deletions, and reassembly into chromothriptically rearranged chromosomes. Whole-genome sequencing of clones with genetically propagatable derivative chromosomes identified complex rearrangements and copy-number alterations that can result in gene inactivation or extrachromosomal gene amplification. We conclude that chromosome segregation errors are sufficient to drive extensive structural variation that recapitulates those commonly associated with human cancers.

Data Use Conditions


See further information on Data Use Conditions

Label Code Version Modifier
general research use DUO:0000042 2021-02-23
institution specific restriction DUO:0000028 2021-02-23
publication required DUO:0000019 2021-02-23
user specific restriction DUO:0000026 2021-02-23