Generation of a Chromosome 8 trisomy through TTK inhibition. (A) Schematic describing two possible ways by which euploidy could be restored in proband cells after treatment with AZ3146. One method consists of the loss of the rearranged copy of Chromosome 8 coupled with the duplication of the remaining chromosome. The second method consists of gaining an unrearranged copy of Chromosome 8 and then subsequently losing the rearranged homolog. (B) Copy numbers of CSMD1 and MICU3 in proband clones treated with AZ3146. Trisomic clones 31 and 33 are labeled with stars. Mean ± SEM; data from representative trials are shown (n ≥ 3 total trials). Genomic DNA from MCF10A cells was used as a diploid control. (C) Karyotypes of two clones that have gained an additional unrearranged copy of Chromosome 8 following AZ3146 treatment.