The lack of LKB1 mutations so far observed in human RAS-driven pancreatic tumors may instead be explained by down-regulation at the protein level, or inactivation of the gene by epigenetic means, because hypermethylation of Lkb1 in hamartomatous polyps and in tumors commonly associated with Peutz–Jeghers syndrome has been demonstrated in the absence of mutation of the gene.34 This evidence concerns the gene STK11 and pancreatic neoplasm.