Meningiomas are the most common tumors of the central nervous system, accounting for about 15% of all primary brain tumors. The most frequent genetic alteration detected in these tumors is in the neurofibromatosis 2 (NF2) tumor suppressor gene. In order to assess the possi­ble role of the N-ras oncogene in meningiomas, we studied 10 frozen biopsies and four paraffin-embedded tissue samples obtained from 14 unrelated Greek patients who had been operated on for meningioma grades I-III. Normal expression of N-ras was detected immunohistochemically in 28.6%, while over-expression was detected in 64.3% of the samples (all grades II or III). In addition, mutation analysis of hot spot codons in two exons of the NF2 gene revealed an Arg®Stop nonsense mutation in four samples that contained mutant N-ras. The interaction between the N-ras and merlin pathways was suggested by the observation that absence of N-ras was detected in a grade I meningioma with an NF2 mutation. Thus, absence of N-ras may decrease the effect of NF2 loss towards advancement of malignancy. These findings provide preliminary evidence for an interaction of the N-ras and the NF2 pathways of cell growth control, and for an important role of N-ras in tumorigenic steps towards malignancy of meningiomas.

Key words: meningioma, neurofibromatosis 2 (NF2), N-ras, oncogenesis