Quantitative analysis of neurofibromatosis type 2 gene transcripts in meningiomas supports the concept of distinct molecular variants.
Meningiomas frequently show mutational inactivation of the neurofibromatosis type 2 tumor suppressor gene (NF2 gene). In a previous study, mutations were preferentially observed in the fibroblastic and transitional subtypes (75%), whereas the meningothelial variant was significantly less affected (25%). To study a potential role of the NF2 gene on the transcriptional level, we have analyzed NF2 transcripts in 67 meningiomas of different subtypes. A competitive reverse transcriptase-PCR assay with an external NF2 gene standard was used for quantitative mRNA analysis. Fibroblastic and transitional meningiomas exhibited significantly lower levels of NF2 mRNA compared with meningothelial variants (p = 0.001, unpaired t test). These data support the concept of a distinct molecular pathway in the formation of meningothelial meningiomas independent from the NF2 gene or its gene product merlin/schwannomin. In addition, in these tumors, NF2 expression was reduced by a factor of 10 (p < 0.001, unpaired t test) in those meningiomas with NF2 gene mutations suggesting decreased stability or impaired transcription of mutated NF2 mRNA. In conclusion, our data provide further evidence for molecular differences between subtypes of meningiomas and support an NF2-independent pathogenesis of meningothelial meningiomas.
Wellenreuther
R
R
Department of Neuropathology, University of Bonn Medical Center, Germany.
Waha
A
A
Vogel
Y
Y
Lenartz
D
D
Schramm
J
J
Wiestler
O D
OD
von Deimling
A
A
D016515:Genes, Neurofibromatosis 2; D014644:Genetic Variation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008577:Meningeal Neoplasms / Q000145:classification / Q000235:genetics*; D008579:Meningioma / Q000145:classification / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D025581:Neurofibromin 2; D014158:Transcription, Genetic
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D025581:Neurofibromin 2