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

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.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001000147 Cancer Genomics
EGAS00001002551 Cancer Genomics

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00000112975 bam 42.3 GB
EGAF00000143605 bam 32.0 GB
EGAF00000143606 bam 32.2 GB
EGAF00000764812 bam 37.6 GB
EGAF00002031089 cram 11.7 GB
EGAF00002031090 cram 11.9 GB
EGAF00002031091 cram 10.8 GB
EGAF00002031092 cram 11.4 GB
EGAF00002031093 cram 11.7 GB
EGAF00002031094 cram 10.6 GB
EGAF00002031095 cram 11.4 GB
EGAF00002031096 cram 11.6 GB
EGAF00002031097 cram 10.6 GB
EGAF00002031098 cram 5.9 GB
EGAF00002031099 cram 6.9 GB
EGAF00002031100 cram 6.4 GB
EGAF00002031101 cram 6.7 GB
EGAF00002031102 cram 6.5 GB
EGAF00002031103 cram 6.0 GB
EGAF00002031104 cram 6.9 GB
EGAF00002031105 cram 6.6 GB
EGAF00002031106 cram 6.9 GB
EGAF00002031107 cram 6.7 GB
EGAF00002031108 cram 6.1 GB
EGAF00002031109 cram 7.1 GB
EGAF00002031110 cram 6.7 GB
EGAF00002031111 cram 6.9 GB
EGAF00002031112 cram 6.8 GB
EGAF00002031113 cram 6.1 GB
EGAF00002031114 cram 7.0 GB
EGAF00002031115 cram 6.7 GB
EGAF00002031116 cram 6.9 GB
EGAF00002031117 cram 6.8 GB
EGAF00002031118 cram 5.9 GB
EGAF00002031119 cram 6.9 GB
EGAF00002031120 cram 6.6 GB
EGAF00002031121 cram 6.8 GB
EGAF00002031122 cram 6.7 GB
EGAF00002031123 cram 8.4 GB
EGAF00002031124 cram 8.9 GB
EGAF00002031125 cram 9.0 GB
EGAF00002031126 cram 8.0 GB
EGAF00002031127 cram 8.5 GB
EGAF00002031128 cram 9.0 GB
EGAF00002031129 cram 9.1 GB
EGAF00002031130 cram 8.1 GB
EGAF00002031131 cram 8.4 GB
EGAF00002031132 cram 9.0 GB
EGAF00002031133 cram 9.1 GB
EGAF00002031134 cram 8.0 GB
EGAF00002031135 cram 15.3 GB
EGAF00002031136 cram 16.5 GB
EGAF00002031137 cram 15.3 GB
EGAF00002031138 cram 16.5 GB
EGAF00002031139 cram 8.4 GB
EGAF00002031140 cram 9.0 GB
EGAF00002031141 cram 8.9 GB
EGAF00002031142 cram 8.0 GB
EGAF00002031143 cram 5.9 GB
EGAF00002031144 cram 6.2 GB
EGAF00002031145 cram 6.7 GB
EGAF00002031146 cram 6.4 GB
EGAF00002031147 cram 6.5 GB
EGAF00002031148 cram 5.9 GB
EGAF00002031149 cram 6.2 GB
EGAF00002031150 cram 6.7 GB
EGAF00002031151 cram 6.4 GB
EGAF00002031152 cram 6.5 GB
EGAF00002031153 cram 6.3 GB
EGAF00002031154 cram 6.5 GB
EGAF00002031155 cram 7.0 GB
EGAF00002031156 cram 6.8 GB
EGAF00002031157 cram 6.8 GB
EGAF00002031158 cram 6.0 GB
EGAF00002031159 cram 6.3 GB
EGAF00002031160 cram 6.7 GB
EGAF00002031161 cram 6.5 GB
EGAF00002031162 cram 6.5 GB
EGAF00002031163 cram 6.3 GB
EGAF00002031164 cram 6.7 GB
EGAF00002031165 cram 7.2 GB
EGAF00002031166 cram 6.8 GB
EGAF00002031167 cram 7.0 GB
EGAF00002031168 cram 14.1 GB
EGAF00002031169 cram 14.7 GB
EGAF00002031170 cram 14.0 GB
EGAF00002031171 cram 14.9 GB
87 Files (832.8 GB)