Methylation analysis of the neurofibromatosis type 1 (NF1) promoter in peripheral nerve sheath tumours

Eur J Cancer. 2004 Dec;40(18):2820-8. doi: 10.1016/j.ejca.2004.07.021.

Abstract

Peripheral nerve sheath tumours are hallmarks of neurofibromatosis type 1 (NF1). Development of plexiform neurofibromas to malignant peripheral nerve sheath tumours (MPNST) is common. The NF1 gene promoter harbours a hypomethylated CpG island. Thus, methylation changes may be involved in the development of different types of neurofibromas and malignant transformation. We investigated NF1-associated dermal (n=9) and plexiform neurofibromas (n=7), MPNST (n=5) and non-NF1 leucocyte samples (n=20) for their methylation pattern by bisulphite genomic sequencing. We could not find global hypermethylation in the NF1 promoter in our series. Nevertheless, site-specific methylation, involving transcription factor binding sites for SP1, CRE (-10), and AP-2, was observed. One region of the 5'-UTR (untranslated region) overlapping with a putative AP-2 binding site was methylated at 30-100% in 4/20 control samples. In conclusion, we did not find hypermethylation in NF1-associated tumours. Instead, low level methylation could parallel a global genomic hypomethylation in malignancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Clone Cells
  • DNA Methylation
  • DNA, Neoplasm / metabolism
  • Female
  • Humans
  • Leukocytes / metabolism
  • Loss of Heterozygosity
  • Male
  • Molecular Sequence Data
  • Nerve Sheath Neoplasms / genetics
  • Nerve Sheath Neoplasms / metabolism*
  • Neurofibromatosis 1 / genetics
  • Neurofibromatosis 1 / metabolism*
  • Polymerase Chain Reaction / methods
  • Promoter Regions, Genetic / genetics*
  • Sulfites / metabolism
  • Transcription, Genetic

Substances

  • Antioxidants
  • DNA, Neoplasm
  • Sulfites
  • sodium bisulfite