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

Hum Genet. 2000 Jul;107(1):33-9. doi: 10.1007/s004390000322.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cloning, Molecular
  • CpG Islands
  • DNA Methylation*
  • Down-Regulation
  • Gene Silencing*
  • Genes, Neurofibromatosis 1 / genetics*
  • Humans
  • Models, Genetic
  • Neurofibromatosis 1 / genetics
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic*
  • Sequence Analysis, DNA
  • Sulfites / metabolism


  • Sulfites