Mutational and Expression Analysis of theNF1Gene Argues Against a Role as Tumor Suppressor in Sporadic Pilocytic Astrocytomas
Open Access
- 1 October 2002
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Neuropathology and Experimental Neurology
- Vol. 61 (10) , 896-902
- https://doi.org/10.1093/jnen/61.10.896
Abstract
Children with neurofibromatosis type I (NF1) have a highly increased risk for developing optic nerve gliomas. Several lines of evidence support the notion that the NF1 gene functions as tumor suppressor in these pilocytic astrocytomas and therefore it is tempting to hypothesize that the NF1 gene plays a similar role in sporadic pilocytic astrocytomas. We searched for possible mechanisms of inactivation of the NF1 gene in pilocytic astrocytomas of different locations. Protein truncation testing (PTT) did not render indication for inactivating mutations in 10 analyzed tumors. Further, loss of heterozygosity analysis revealed maintenance of heterozygosity for 3 intragenic markers in 11 informative cases. Using a real-time PCR-based assay we showed that total NF1 transcript levels are high in pilocytic astrocytomas and that the NF1 type I and type II expression ratios in pilocytic astrocytomas are comparable to ratios in normal brain tissue and high-grade gliomas. Consequently, the data presented here argue against altered NF1 gene expression and the involvement of the NF1 gene in the tumorigenesis of sporadic pilocytic astrocytomas.Keywords
This publication has 33 references indexed in Scilit:
- Heterozygosity for the neurofibromatosis 1 (NF1) tumor suppressor results in abnormalities in cell attachment, spreading and motility in astrocytesHuman Molecular Genetics, 2001
- Loss ofNF1Alleles Distinguish Sporadic from NF1-Associated Pilocytic AstrocytomasJournal of Neuropathology and Experimental Neurology, 2001
- Loss of neurofibromatosis 1 (NF1) gene expression in NF1‐associated pilocytic astrocytomasNeuropathology and Applied Neurobiology, 2000
- Haploinsufficiency for the neurofibromatosis 1 (NF1) tumor suppressor results in increased astrocyte proliferationOncogene, 1999
- Confirmation of a Double-Hit Model for the NF1Gene in Benign NeurofibromasAmerican Journal of Human Genetics, 1997
- The Diagnostic Evaluation and Multidisciplinary Management of Neurofibromatosis 1 and Neurofibromatosis 2JAMA, 1997
- Benign neurofibromas in type 1 neurofibromatosis (NF1) show somatic deletions of the NF1 geneNature Genetics, 1995
- Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesisNature Genetics, 1993
- A conserved alternative splice in the von Recklinghausen neurofibromatosis (NF1) gene produces two neurofibromin isoforms, both of which have GTPase-activating protein activity.Molecular and Cellular Biology, 1993
- Brain tumors predominantly express the neurofibromatosis type 1 gene transcripts containing the 63 base insert in the region coding for GTPase activating protein-related domainBiochemical and Biophysical Research Communications, 1991