title: Microsatellite instability and promoter methylation as possible causes of NF1 gene inactivation in neurofibromas.
abstract: Neurofibromatosis type 1 (NF1) is a frequent hereditary disorder. One of the characteristic features of this disease is the development of neurofibromas. Since the NF1 gene is supposed to be a tumour suppressor gene, these neurofibromas should develop upon inactivation of both NF1 alleles. So far, mutation and deletion have been found to be involved in NF1 gene inactivation. However, these inactivating mechanisms explain the development of only a limited fraction of analysed neurofibromas. In this study, we investigated microsatellite instability (MSI) and promoter methylation as potential contributors to NF1 gene inactivation. As site-specific methylation in the NF1 promoter inhibits binding of transcription factors Sp1 and CREB, we studied the methylation status of their binding sites in particular. We analysed 20 neurofibromas and three neurofibrosarcomas, but did not find evidence for microsatellite instability or NF1 promoter methylation in any of the tumours. Thus, our data suggest that both microsatellite instability and promoter methylation are unlikely to be the major causes of NF1 gene inactivation in these tumours.
authors.affiliation: Department of Human Genetics, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Luijten
authors.forename: S
authors.initials: S
authors.lastname: Redeker
authors.forename: M M
authors.initials: MM
authors.lastname: van Noesel
authors.forename: D
authors.initials: D
authors.lastname: Troost
authors.forename: A
authors.initials: A
authors.lastname: Westerveld
authors.forename: T J
authors.initials: TJ
authors.lastname: Hulsebos
mesh_terms: D001483:Base Sequence; D051786:Cyclic AMP Response Element Modulator; D004247:DNA / Q000032:analysis; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009455:Neurofibroma / Q000235:genetics*; D025542:Neurofibromin 1; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D051786:Cyclic AMP Response Element Modulator; D004247:DNA