SHP2 is a well-established major regulator of RAS-to-RAF-to-MAPK signal pathway and somatic gain-of-function SHP2 mutations or overexpression have also been identified in several hematologic malignancies as well as solid tumors such as gastric, breast, lung and pancreatic cancers and RASopathies1,2,6,23–25. This evidence concerns the gene RAF1 and familial pancreatic carcinoma.