A survey of CIN measures across mechanistic models

Cancer relies on genomic changes to drive evolution. One type of change, Chromosomal INstability (CIN), promotes plasticity and heterogeneity of chromosome sets via ongoing errors in mitosis. The rate of these errors informs patient prognosis, drug response, and risk of metastasis. However, measuring CIN in patient tissues is challenging, hindering the emergence of CIN rate as a prognostic and predictive clini-cal biomarker. To advance clinical measures of CIN, we quantitatively tested the relative performance of several CIN measures in tandem using four well-defined, inducible CIN models. This survey revealed poor sensitivity in several common CIN assays and highlights the primacy of single-cell approaches. Further, we propose a standard, normalized unit of CIN, permitting comparison across methods and studies.