Loss of neurofibromin is associated with activation of RAS/MAPK and PI3-K/AKT signaling in a neurofibromatosis 1 astrocytoma.

摘要: Neurofibromatosis 1 (NF1) is a common autosomal dominant cancer predisposition syndrome, in which 15% to 20% of affected individuals develop astrocytomas. Neurofibromin, the protein product NF1 gene, functions as tumor suppressor, largely by inhibiting Ras activity. While loss neurofibromin has been implicated molecular pathogenesis other NF1-associated tumors, there no formal evidence demonstrating function In this report, we describe an patient from whom both astrocytoma tissue well corresponding non-neoplastic white matter were available for analysis. Loss expression was observed and associated with elevated levels Ras-GTP. However, Ras-GTP not result oncogenic mutations, altered p120-GAP function, growth factor receptor activation, or abnormal p53, Rb, p16 expression. Furthermore, increased Raf-MAPK PI3-K/Akt activity detected compared normal matter. These results support role critical GAP