POLE and neoplasm: Next, our analysis suggests various associations of differential NMD efficiency to tumor evolution (Fig. 6A): shaping selective pressures on tumor suppressor genes, with prominent effects on SMAD4, TP53, and APC. In a cancer-type specific analysis, we observed a similar trend in hypermutated tumors like stomach MSI, colon MSI, POLE-mutant uterus, and also lung cancers, where these TSGs were more frequently mutated.