Half of MPNST occur in patients with the cancer predisposition syndrome NF1, caused by germline loss of function (LOF) of one copy of the tumor suppressor gene NF1. In patients with NF1, most MPNST arise from within plexiform neurofibromas (pNF), which are pre-malignant tumors of the peripheral nerve [3,4,5]. The gene discussed is NF1; the disease is plexiform neurofibroma.