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

TY - JOUR

T1 - Quantitative analysis of NF1 and OMGP gene transcripts in sporadic gliomas, sporadic meningiomas and neurofibromatosis type 1-associated plexiform neurofibromas

AU - Peters, N

AU - Waha, A

AU - Wellenreuther, R

AU - Friedrich, R E

AU - Mautner, V F

AU - Hoffmeyer, S

AU - Lenartz, D

AU - Schramm, J

AU - Wiestler, O D

AU - von Deimling, A

PY - 1999/6/1

Y1 - 1999/6/1

N2 - The close association of neurofibromatosis type 1 (NF1) with gliomas raises the question of whether the NF1 gene may be involved in the pathogenesis of sporadic astrocytic brain tumors. However, no frequent mutations within NF1 have been described in these tumors. Recent data on a limited series of gliomas indicate that NF1 expression may even be increased, thereby questioning 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 transcription 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 different malignancy stages of astrocytomas. As expected, the plexiform neurofibromas showed only very low NF1 expression. A striking finding was the highly variable expression of those genes selected to serve as references. While B2M and ACTB exhibited comparable levels of expression within different grades of astrocytomas and meningiomas, GAPD showed an inverse pattern in these tumors. In conclusion, NF1 expression is strongly reduced in NF1-associated plexiform neurofibromas but not in astrocytic tumors. The significant differences between B2M, ACTB and GAPD transcript levels brings into question the common practice of defining gene expression as a ratio between the transcripts of interest and those of these reference genes.

AB - The close association of neurofibromatosis type 1 (NF1) with gliomas raises the question of whether the NF1 gene may be involved in the pathogenesis of sporadic astrocytic brain tumors. However, no frequent mutations within NF1 have been described in these tumors. Recent data on a limited series of gliomas indicate that NF1 expression may even be increased, thereby questioning 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 transcription 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 different malignancy stages of astrocytomas. As expected, the plexiform neurofibromas showed only very low NF1 expression. A striking finding was the highly variable expression of those genes selected to serve as references. While B2M and ACTB exhibited comparable levels of expression within different grades of astrocytomas and meningiomas, GAPD showed an inverse pattern in these tumors. In conclusion, NF1 expression is strongly reduced in NF1-associated plexiform neurofibromas but not in astrocytic tumors. The significant differences between B2M, ACTB and GAPD transcript levels brings into question the common practice of defining gene expression as a ratio between the transcripts of interest and those of these reference genes.

KW - Base Sequence

KW - Brain Neoplasms

KW - GPI-Linked Proteins

KW - Genes, Neurofibromatosis 1

KW - Glioma

KW - Humans

KW - Meningeal Neoplasms

KW - Meningioma

KW - Molecular Sequence Data

KW - Myelin Proteins

KW - Myelin-Associated Glycoprotein

KW - Myelin-Oligodendrocyte Glycoprotein

KW - Neurofibromatosis 1

KW - Polymerase Chain Reaction

KW - Transcription, Genetic

M3 - SCORING: Journal article

C2 - 10378372

VL - 97

SP - 547

EP - 551

JO - ACTA NEUROPATHOL

JF - ACTA NEUROPATHOL

SN - 0001-6322

IS - 6

ER -