Fifty percent of Noonan syndrome patients and 35% of JMML cases carry gain-of-function mutations in PTPN11 (protein-tyrosine phosphatase, non-receptor-type, 11), altering SHP-2, a tyrosine phosphatase involved in the regulation of the RAS/MAPK pathway (64). Here, PTPN11 is linked to juvenile myelomonocytic leukemia.