Chromosome instability (CIN) is defined as an increased rate of chromosome gains and losses that manifests as cell-to-cell karyotypic heterogeneity and drives cancer initiation and evolution. Current research efforts are aimed at identifying the etiological origins of CIN, establishing its roles in cancer pathogenesis, understanding its implications for patient prognosis, and developing novel therapeutics that are capable of exploiting CIN. Thus, the ability to accurately identify and evaluate CIN is critical within both research and clinical settings. Here, we provide an overview of quantitative single cell approaches that evaluate and resolve cell-to-cell heterogeneity and CIN, and discuss considerations when selecting the most appropriate approach to suit both research and clinical contexts.

• Chromosome instability (CIN) is prevalent and dynamic in high-grade serous ovarian cancer (HGSOC). • Quantitative imaging microscopy reveals 91% of ascites (26 samples) and 100% of solid tumours (36 samples) exhibit CIN. • CIN increases with disease progression and decreases following chemotherapy treatment. • Higher levels of CIN occur in solid tumour samples relative to patient-matched ascites samples. • Data suggest that cells with lower levels of CIN may be more amendable to metastatic spread.