Figure 6:

Hypothesized model of clonal microsatellite instability. In this model, mismatch repair deficiency leading to MSI develops early in tumor evolution, and is present in the founding tumor cell and all descendent subclones. As MMRd is stochastic, it introduces insertions and deletions at different loci in different cells, which fosters tumor heterogeneity. MMRd continues to cause MSI throughout the development of the cancer, which increases the level of microsatellite divergence within subclones over time. Instability at specific loci is preserved and expanded within the progeny of affected cells.