Consistent with this prediction, a fifth of the nonsense mutations observed in the 369 cancer genes occurred in just 8 tumor suppressor genes (APC, ATM, PTEN, MGA, PIK3R1, ARID1A, NF1, and FAT1)—all target genes expected for the tumor types where POLE mutations arise, namely colorectal and endometrial cancers. This evidence concerns the gene PIK3R1 and cancer.