Quantitative analysis of NF1 and OMGP gene transcripts in sporadic gliomas, sporadic meningiomas and neurofibromatosis type 1-associated plexiform neurofibromas

The close association of neurofibromatosis type 1 (NF1) with gliomas raises the question of whether the NF1 gene may be involved in the pathogenesis o f sporadic astrocytic brain tumors. However, no frequent mutations within N F1 have been described in these tumors. Recent data on a limited series of gliomas indicate that NF1 expression may even be increased, thereby questio ning the role of NF1 as a tumor suppressor in astrocytomas. In the present study, we examined the expression of NF1 in a series of 96 tumors including astrocytomas, meningiomas and plexiform neurofibromas. NF1 RNA transcripti on levels were compared to those of the reference genes B2M, ACTB and GAPD. The expression of OMGP, which is interposed in the NF1 gene, served as an additional control. NF1 expression did not significantly diverge among diff erent malignancy stages of astrocytomas. As expected, the plexiform neurofi bromas showed only very low NF1 expression. A striking finding was the high ly variable expression of those genes selected to serve as references. Whil e B2M and ACTB exhibited comparable levels of expression within different g rades of astrocytomas and meningiomas, GAPD showed an inverse pattern in th ese tumors. In conclusion, NF1 expression is strongly reduced in NF1-associ ated plexiform neurofibromas but not in astrocytic tumors. The significant differences between B2M, ACTB and GAPD transcript levels brings into questi on the common practice of defining gene expression as a ratio between the t ranscripts of interest and those of these reference genes.