Cell culture and drug treatment

RPE1 and MCF7 (American Type Culture Collection) cells were grown in DMEM supplemented with 10% FBS and 100 units/ml penicillin and 100 μg/ml streptomycin. HT29 cells were growth in McCoy media supplemented with 10% FBS and Pen/Strep as above. Aneuploid cells RPE1 with trisomy 12 and trisomy 5 (Ts12 Ts5) and RPE1 hTert cells were kindly provided by the Storchova laboratory (Stingele et al, 2012 (link)). Most drugs used in this study were synthesized by Syncom B.V., except for AZD8055 (Sigma-Aldrich), EPZ015666 (Sigma-Aldrich) and SKI-1 (Abcam). All drugs were dissolved in DMSO (Sigma-Aldrich) and diluted in tissue culture medium as indicated. Used drug concentrations were titrated before the actual screen, starting from an initial drug concentration of 10 μM. If the initial drug concentration of 10 μM was (near-)toxic to wild-type RPE1 cells, the cells were next exposed to 1 μM, 0.1 μM, 10 nM, or 1 nM of the compound, until a concentration was found that was no longer toxic (see Supplemental Data 3 for all initial drug titration growth curves).