Following early TP53 mutations or E2F‐mediated G1 arrest defects in p53 wild‐type cancer, the odds of tetraploidization in cancer cells increase,[6] whereas G1 arrest following tetraploidization can be overridden by cyclin D overexpression.[61] Furthermore, the presence of extra centrosomes and increased cell size in tetraploid cells triggers the tumor suppressor Hippo‐YAP pathway, which involves altered small G protein signaling, including RAC1 and RHOA. The gene discussed is TP53; the disease is cancer.