For example, loss of or mutation in neurofibromin 1 (NF1 that encodes GAP) in neurofibromatosis type 1 (ref. 12), mutation in SHP2 (also known as PTPN11 that encodes protein tyrosine phosphatase) in juvenile myelomonocytic leukaemia13, and the overexpression of growth factor receptors in breast cancer14 and glioblastoma multiforme (GBM)15 have been associated with the hyperactivation of wild-type (WT) Ras. Here, PTPN11 is linked to neurofibromatosis type 1.