Proteogenomic analysis reveals adaptive strategies for alleviating the consequences of aneuploidy in cancer.

Aneuploidy is prevalent in cancer, conferring fitness advantage, multidrug resistance, and poor prognosis. In contrast, experimentally induced aneuploidy often results in adverse effects and impaired proliferation. This paradox underscores the necessity of cancer cells to adapt to abnormal chromosome numbers. To identify molecular mechanisms of adaptation to aneuploidy, we initiated in vitro evolution of cells with extra chromosomes added via microcell-mediated chromosome transfer. To this end, we cultured cells in a nutrient-rich medium for 50 passages or plated the cells at a low density and selectively collected the largest colonies originating from a single cell (colony selection). The analysis of somatic copy number variations in the evolved cell lines was then carried out based on whole genome sequencing (WGS) and array-based comparative genomic hybridization (aCGH).