Biallelic loss of BRCA function is associated with a higher response to DNA-damaging agents. Nevertheless, inactivating mechanisms of the wild-type BRCA1 allele are poorly understood in patients with pancreatic ductal adenocarcinoma and a germline BRCA1 variant.

Epigenetic silencing via BRCA1 promotor methylation has been reported in ovarian and breast tumors, but not in pancreatic ductal adenocarcinoma. By applying a methylation array and pyrosequencing, we observed BRCA1 promotor hypermethylation was a distinctly uncommon mechanism of wild-type BRCA1 allele inactivation in patients with germline BRCA1-pancreatic ductal adenocarcinoma.