MPNST : Molecular Genetics
Malignant peripheral nerve sheath tumors (MPNST), both sporadic as well as those arising in neurofibromatosis 1, show inactivation of tumor suppressor gene NF1 at 17q11.2. NF1 codes for Neurofibromin that is expressed in brain and peripheral nerves. It is a RAS GTPase-activating protein that negatively regulates (inactivates) RAS proteins. Loss of NF1 function promotes RAS activity which activates downstream signaling pathways leading to tumor formation. In NF1 patients, the progression from neurofibroma to MPNST is frequently associated with gains involving 17q, 7p, 5p, 8q, and 12q. In addition, there may be losses involving 9p, 13q, and 1p. CDKN2 on 9p is linked to two protein products: p16 (which regulates cell cycle through Rb pathway) and p19 (which regulates cell cycle through p53 pathway). Immunostain for p53 is consistently positive in majority of the MPNSTs.