The cells remaining at the primary tumor site evolved with a higher mutation rate after acquiring the mutations of UBR5 and RAD21. We can also observe a further mutation rate increase after a group of cells acquired mutation of RSPO2. Although the direct relationship between these proteins and changes in mutation rate is not studied in the literature, Li et al. [54] show that there is a correlation between elevated expression of RSPO2 in RNA samples of Patient Derived Xenograft models with colorectal cancer. This evidence concerns the gene RSPO2 and colorectal cancer.