An association analysis of cancer genomic scores jointly with CRISPR/RNAi genetic screening data identified an additional common TP53-loss phenocopying gene, USP28. Deletions in USP28 are associated with a TP53 functional impairment in 2.9–7.6% of breast, bladder, lung, liver and stomach tumors, and have comparable effect size to MDM4 amplifications. Here, MDM4 is linked to gastric neoplasm.