Figure 2. Epigenetic disruption of the centromere and implications for chromosomal instability (CIN). (A): Schematic representation of centromere disruption pathways by CENP-A upregulation and heterochromatization. B: HP1 depletion causes that localization of Misc12C to the kinetochore is reduced, which may promote microtubule misincorporation and kinetochore unsteadiness generating aneuploidy and CIN. C: Chromosomal instability generated by different mechanisms at centromeric and pericentromeric regions as a plausible early cause of cancer.