Analysis of genome-doubled breast cancer revealed an enrichment of mutations in TP53 (ref. 37), but not in PIK3CA. However, PIK3CA mutations in these cancers were found to generally precede the genome doubling event and to exhibit a significant tendency for mutual exclusivity with TP53. These data are consistent with a PIK3CA tolerance mechanism to genome doubling, acting independently of TP53 inactivation. The gene discussed is PIK3CA; the disease is breast cancer.