A clinical proteogenomic analysis of 100 pancreatic ductal adenocarcinoma samples was able to precisely identify mutations in TP53, KRAS, SMAD4, CDKN2A, ARID1A, and ROBO2, including mutations in the KDM6A and PREX2 driver genes, which drive PDAC tumorigenesis. This evidence concerns the gene KDM6A and pancreatic ductal adenocarcinoma.