These results are in line with recent findings in yeast pol2-P301R cells (33) and in POLE P286R-driven mouse cancer models (42), and suggest that a transition to the diploid or polyploid state facilitates survival in the face of extreme mutagenesis as expected from the fact that deleterious mutations are frequently recessive and often masked in a heterozygotic diploid state. The gene discussed is POLE; the disease is cancer.