Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1

Genes Chromosomes Cancer. 2000 Aug;28(4):425-31.


Neurofibromatosis type 1 (NF1) is a common autosomal dominant condition characterized by benign tumor (neurofibroma) growth and increased risk of malignancy. Dermal neurofibromas, arising from superficial nerves, are primarily of cosmetic significance, whereas plexiform neurofibromas, typically larger and associated with deeply placed nerves, extend into contiguous tissues and may cause serious functional impairment. Malignant peripheral nerve sheath tumors (MPNSTs) seem to arise from plexiform neurofibromas. The NF1 gene, on chromosome segment 17q11.2, encodes a protein that has tumor suppressor function. Loss of heterozygosity (LOH) for NF1 has been reported in some neurofibromas and NF1 malignancies, but plexiform tumors have been poorly represented. Also, the studies did not always employ the same markers, preventing simple comparison of the frequency and extent of LOH among different tumor types. Our chromosome 17 LOH analysis in a cohort of three tumor types was positive for NF1 allele loss in 2/15 (13%) dermal neurofibromas, 4/10 (40%) plexiform neurofibromas, and 3/5 (60%) MPNSTs. Although the region of loss varied, the p arm (including TP53) was lost only in malignant tumors. The losses in the plexiform tumors all included sequences distal to NF1. No subtle TP53 mutations were found in any tumors. This study also reports the identification of both NF1 "hits" in plexiform tumors, further supporting the tumor suppressor role of the NF1 gene in this tumor type.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chromosomes, Human, Pair 17 / genetics*
  • Genes, Neurofibromatosis 1 / genetics
  • Genes, p53 / genetics
  • Genetic Markers
  • Humans
  • Loss of Heterozygosity / genetics*
  • Middle Aged
  • Neurofibroma / genetics
  • Neurofibroma, Plexiform / genetics
  • Neurofibromatosis 1 / genetics*
  • Peripheral Nervous System Neoplasms / genetics
  • Skin Neoplasms / genetics


  • Genetic Markers