USP22 and cancer: Remarkably, diminished expression of USP22 and/or overexpression of RNF20/40 at the mRNA level is observed in 38% of primary tumors in colorectal adenocarcinoma [37,48] (Figure 4), a cancer type characterized by a very high prevalence of chromosome instability (up to 85% of cases) [96,97,98,99].