PTPN11 and RASopathy: Mutations regarding regulatory proteins of RAS have also been implicated in enhancing tumorigenesis as well as development of therapy resistance and include NF1. NF1 is frequently co-mutated with codon 13 mutations of KRAS and PTPN11. PTPN11 encodes the Src homology region 2 domain-containing phosphatase-2 (SHP2) and can lead to so-called RASopathies, i.e., clinically defined genetic syndromes caused by germline mutations of regulators or components of the MAPK pathway (100).