Schwann cells harbor the somatic NF1 mutation in neurofibromas

Evidence of two different Schwann cell subpopulations

Eduard Serra, Thorsten Rosenbaum, Ursula Winner, Rosa Aledo, Elisabet Ars, Xavier P. Estivill, Hans Gerd Lenard, Conxi Lázaro

Research output: Contribution to journalArticle

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Abstract

Neurofibromas are one of the most characteristic features of neurofibromatosis type 1 (NF1), an inherited autosomal-dominant neurogenetic disorder affecting 1 in 3500 individuals worldwide. These benign tumors mainly consist of Schwann cells (SCs) and fibroblasts. Recent evidence demonstrates that somatic mutations at the NF1 gene are found in neurofibromas, but it has not been demonstrated whether SCs, fibroblasts and/or both cell types bear a somatic loss of NF1. We recently established a cell culture system that allows selective expansion of human SCs from neurofibromas. We cultured pure populations of SCs and fibroblasts derived from 10 neurofibromas with characterized NF1 mutations and found that SCs but not fibroblasts harbored a somatic mutation at the NF1 locus in all studied tumors. Furthermore, by culturing neurofibroma-derived SCs under different in vitro conditions we were able to obtain two genetically distinct SC subpopulations: NF1(-/-) and NF1(+/-). These data strongly support the idea that NF1 mutations in SCs, but not in fibroblasts, correlate to neurofibroma formation and demonstrate that only a portion of SCs in neurofibromas have mutations in both NF1 alleles.

Original languageEnglish
Pages (from-to)3055-3064
Number of pages10
JournalHuman Molecular Genetics
Volume9
Issue number20
Publication statusPublished - 12 Dec 2000
Externally publishedYes

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Neurofibroma
Neurofibromatosis 1
Schwann Cells
Mutation
Fibroblasts
Neurofibromatosis 1 Genes
Neoplasms
Cell Culture Techniques
Alleles

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Schwann cells harbor the somatic NF1 mutation in neurofibromas : Evidence of two different Schwann cell subpopulations. / Serra, Eduard; Rosenbaum, Thorsten; Winner, Ursula; Aledo, Rosa; Ars, Elisabet; Estivill, Xavier P.; Lenard, Hans Gerd; Lázaro, Conxi.

In: Human Molecular Genetics, Vol. 9, No. 20, 12.12.2000, p. 3055-3064.

Research output: Contribution to journalArticle

Serra, E, Rosenbaum, T, Winner, U, Aledo, R, Ars, E, Estivill, XP, Lenard, HG & Lázaro, C 2000, 'Schwann cells harbor the somatic NF1 mutation in neurofibromas: Evidence of two different Schwann cell subpopulations', Human Molecular Genetics, vol. 9, no. 20, pp. 3055-3064.
Serra, Eduard ; Rosenbaum, Thorsten ; Winner, Ursula ; Aledo, Rosa ; Ars, Elisabet ; Estivill, Xavier P. ; Lenard, Hans Gerd ; Lázaro, Conxi. / Schwann cells harbor the somatic NF1 mutation in neurofibromas : Evidence of two different Schwann cell subpopulations. In: Human Molecular Genetics. 2000 ; Vol. 9, No. 20. pp. 3055-3064.
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