Binary Karyotypes Are Universally Selected for across Cancers

Aneuploid karyotype evolution leads to immense variability in cancer prognosis and drug response, yet the general principles governing its evolution are still missing. Here, by visualizing aneuploidy patterns in a novel way, we identify a universal selection principle for karyotypes composed of two chromosome copy numbers states, termed binary karyotypes. These karyotypes make up over three-quarters of the Mitelman database, which our model explains by increased fitness relative to other aneuploid karyotypes. We find that binary karyotypes do not require p53 inactivation and have distinct expression of genes related to fitness, providing biological basis for our model prediction. Furthermore, we show that patients with binary karyotypes have higher survival rates. Taken together, our results reveal binary karyotypes as a distinct category of aneuploid karyotypes that are universally selected for independent of encoded genes or any other chromosome-specific feature, refining the current paradigm of aneuploid cell classification.