Abstract Most clinical mutations of TP53 are missense mutations. We previously showed that TP53-missense mutations common in triple-negative breast cancer (TNBC) patients produce neomorphic phenotypes compared to TP53-null cells, with the TAZ/TEAD pathway strongly associated with cell invasion in aggressive p53 mutants. But TP53 mutations alone are insufficient for full oncogenesis. We performed a genome-wide CRISPR screen to identify "co-drivers" of the weakly aggressive p53 mutation, Y234C.
