Likewise, the proportion of cases displaying a mutational signature 3 was significantly higher in the 12 PALB2-associated breast cancers with bi-allelic inactivation sequenced by WES than in the 491 ER−/HER2− and ER+/HER2− non-BRCA1/2/PALB2-associated breast cancers for which mutational signatures could be inferred (67% vs. 17%; P = 0.0002, Fisher’s exact test; P = 0.02, bootstrapping-corrected; Fig. 4c). The gene discussed is ESR1; the disease is breast cancer.