BRCA1 and esophageal squamous cell carcinoma: Loss of heterozygosity (LOH) at the BRCA1/2 loci was detected in six out of the seven patients with BRCA1/2 alterations that exhibited high signature 3 level, highlighting the clinical link between the biallelic inactivation of BRCA1/2 and signature 3 in ESCC (Fig. 4a, b).