title: Hypermethylation of the neurofibromatosis type 1 (NF1) gene promoter is not a common event in the inactivation of the NF1 gene in NF1-specific tumours.
abstract: Neurofibromatosis type 1 (NFI) is a common autosomal dominant disorder characterised by café-au-lait spots, neurofibromas and iris hamartomas. Since the NF1 gene product neurofibromin contains a GAP-related domain involved in the down-regulation of p21(ras) oncogene activity, the NF1 gene has come to be regarded as a tumour-suppressor gene. One common mechanism of tumour-suppressor gene inactivation during tumorigenesis is promoter hypermethylation, this "epi-mutation" being functionally equivalent to a second-hit somatic mutation. To assess the importance of promoter hypermethylation in NF1 gene inactivation in NF1-related tumours, the methylation status of the NF1 promoter region was determined by bisulphite-modified genomic sequencing in NF1-specific tumours and peripheral blood lymphocytes (PBL) from both NF1 patients and normal controls. Tumour-specific CpG methylation of six distinct CpG sites was identified at positions -609, -429, 406, -383, -331 and -315 relative to the transcriptional start site. However, since all other CpG sites were unmethylated in all tissues examined, it is unlikely that CpG hypermethylation within the NF1 promoter represents a common mutational mechanism leading to neurofibroma formation.
authors.affiliation: Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, Wales, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Horan
authors.forename: D N
authors.initials: DN
authors.lastname: Cooper
authors.forename: M
authors.initials: M
authors.lastname: Upadhyaya
mesh_terms: D016022:Case-Control Studies; D003001:Cloning, Molecular; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D020868:Gene Silencing; D016514:Genes, Neurofibromatosis 1 / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D009456:Neurofibromatosis 1 / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D013447:Sulfites / Q000378:metabolism
chemical_list: D013447:Sulfites