Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Single-cell PCR performed with neurofibroma Schwann cells reveals the presence of both alleles of the neurofibromatosis type 1 (NF1) gene

  • 40 Accesses

  • 8 Citations

Abstract

It is commonly held that Schwann cells (SC) are the progenitor cells of benign neurofibromas. To test for loss of heterozygosity (LOH) at the neurofibromatosis 1 (NF1) gene locus, three intragenic polymorphic markers were analyzed after polymerase chain reaction amplification, starting from 98 single SC isolated from primary cultures of neurofibromas of five informative NF1 patients. The patterns obtained did not provide evidence for LOH at the NF1 gene. LOH by nondisjunction, large deletions, or somatic recombination in SC seems not to be the mechanism of generation of neurofibromas.

This is a preview of subscription content, log in to check access.

References

  1. Ballester R, Marchuk DA, Boguski M, Sauline AM, Letcher R, Wigler M, Collins FS (1990) The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell 63:851–859

  2. Bochkov NP, Kuleshov NP, Chebotarev AN, Alekhin VI, Midian SA (1974) Population cytogenetic investigation of newborns in Moscow. Humangenetik 22: 139–152

  3. Cawthon RM, Weiss R, Xu G, Viskochil D, Culver M, Stevens J, Robertson M, Dunn D, Gesteland R, O'Connell P, White R (1990) A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and protein mutations. Cell 62: 193–201

  4. Erlandson RA (1985) Peripheral nerve sheath tumors. Ultrastruct Pathol 9:113–122

  5. Fialkow PJ, Sagebiel RW, Garther SM, Rimoin DL (1971) Multiple cell origin of hereditary neurofibromas. N Engl J Med 284: 298–300

  6. Goldgar DE, Green P, Parry DM, Mulvihill JJ (1989) Multipoint linkage analysis in neurofibromatosis type I: an international collaboration. Am J Hum Genet 44:6–12

  7. Hoffmeyer S, Assum G (1994) An RsaI polymorphism in the transcribed region of the neurofibromatosis (NF1)-gene. Hum Genet 93:481–482

  8. Hoffmeyer S, Assum G, Kaufmann D, Schwenk K, Krone W (1994) A deletion in the 5′-region of the neurofibromatosis type l (NF1) gene. Hum Genet 94:97–100

  9. Huson SM, Hughes RAC (1994) The neurofibromatoses: a pathogenetic and clinical overview. Chapman & Hall Medical, London Glasgow New York Tokyo Melbourne Madras

  10. Kamata Y (1978) Study of the ultrastructure and acetylcholinesterase activity in von Recklinghausen's neurofibromatosis. Acta Pathol Jpn 28: 393–110

  11. Kim SU, Yong VW, Watanabe K, Shin DH (1989) Human fetal Schwann cells in culture: phenotypic expressions and proliferative capability. J Neurosci Res 22:50–59

  12. Knudson AG (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823

  13. Krone W, Jirikowski G, Mühleck O, Kling H, Gall H (1983) Cell culture studies on neurofibromatosis (von Recklinghausen). II. Occurrence of glial cells in primary cultures of peripheral neurofibromas. Hum Genet 63:247–251

  14. Lasko D, Cavenee W (1991) Loss of constitutional heterozygosity in human cancer. Annu Rev Genet 25:281–314

  15. Lothe RA, Sauter G, Danielsen HE, Stenwig AE, Hylein B, O'Connell P, Borresen AL (1993) Genetic alterations in a malignant Schwannoma from a patient with neurofibromatosis (NF1). Pathol Res Pract 189:465–471

  16. Lázaro C, Gaona A, Xu G, Weiss R, Estévill X (1993) A highly informative CA/GT repeat polymorphism in intron 38 of human neurofibromatosis type 1 (NF1) gene. Hum Genet 92: 429–430

  17. Li Y, O'Connell P, Huntsman-Breidenbach H, Cawthon RM, Stevens J, Xu G, Neil S, Robertson M, White R, Viskochil D (1995) Genomic organization ot the neurofibromatosis 1 gene (NF1). Genomics 25:9–18

  18. Marchuk DA, Saulino AM, Tavakkol R, Swaroop M, Wallace MR, Andersen LB, Mitchell AL, Gutmann DH, Boguski M, Collins FS (1991) cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product. Genomics 11:931–940

  19. Martin GA, Viskochil D, Bollag G, McCabe PC, Crosier WJ, Haubruck H, Conroy L, Clark R, O'Connell P, Cawthon RM, Innis MA, McCormick F (1990) The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell 63:843–849

  20. Menon AG, Anderson KM, Riccardi VM, Chung RY, Whaley JM, Yandell DM, Farmer GE, Freiman RN, Lee JK, Li FP, Baker DF, Ledbetter DH, Kleider A, Martuza RL, Gusella JF, Seizinger BR (1990) Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. Proc Natl Acad Sci USA 87:5435–5439

  21. Peltonen J, Jaakkola S, Lebwohl M, Renvall S, Risteli L, Virtanen I, Uitto J (1988) Cellular differentiation and expression of matrix genes in type 1 neurofibromatosis. Lab Invest 59:760–771

  22. Porter S, Clark MB, Glaser L, Bunge RP (1986) Schwann cells stimulated to proliferate in the absence of neurons retain full functional capability. J Neurosci 6:3070–3078

  23. Riccardi VM (1992) Neurofibromatosis: phenotype, natural history, and pathogenesis, 2nd edn. The Johns Hopkins University Press, Baltimore

  24. Rutkowski JL, Needham L, Frayer K, Carson D, McKhann G, Tennekoon GI (1990) Evidence that secondary rat Schwann cells in culture maintain their differentiated phenotype. J Neurochem 54:1895–1904

  25. Rutkowski JL, Tennekoon GJ, Gillicuddy JE (1992) Selective culture of mitotically active human Schwann cells from adult sural nerves. Ann Neurol 31:580–586

  26. Rutkowski JL, Kirk CJ, Lerner MA, Tennekoon GI (1995) Purification and expansion of human Schwann cells in vitro. Nature Medicine 1:80–83

  27. Scarpini E, Kreider BQ, Lisak RP, Meola G, Velicogna ME, Baron P, Beretta S, Buscaglia M, Ross AH, Scarlato G (1988) Cultures of human Schwann cells isolated from fetal nerves. Brain Res 440:261–266

  28. Skuse GR, Kosciolek BA, Rowley PT (1989) Molecular genetic analysis of tumors in von Recklinghausen neurofibromatosis: loss of heterozygosity for chromosome 17. Genes Chromosom Cancer 1:36–41

  29. Stark M, Assum G, Kaufmann D, Kehrer H, Krone W (1992) Analysis of segregation and expression of an identified mutation at the neurofibromatosis type 1 locus. Hum Genet 90:356–359

  30. Stefansson K, Wollmann R, Jerkovic M (1982) S-100 protein in soft-tissue tumors derived from Schwann cells and melanocytes. Am J Pathol 106:261–268

  31. Viskochil D, Buchberg AM, Xu G, Cawthon RM, Stevens J, Wolff RK, Culver M, Carey JC, Copeland NG, Jenkins NA, White R, O'Connell P (1990) Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 62: 187–192

  32. Waggener JD (1966) Ultrastructure of benign peripheral nerve sheath tumors. Cancer 19:699–709

  33. Wallace MR, Marchuk DA, Anderson LB, Letcher R, Odeh HM, Saulino AM, Fountain JW, Brereton A, Nicholson J, Mitchell AL, Brownstein BH, Collins FS (1990) Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249:181–186

  34. Xu G, O'Connell P, Viskochil D, Cawthon RM, Robertson M, Culver M, Dunn D, Stevens J, Gesteland R, White R, Weiss R (1990) The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62:599–608

  35. Xu G, Nebon L, O'Connell P, White R (1991) An alu-polymorphism intragenic to the neurofibromatosis type 1 gene (NF1). Nucleic Acids Res 19:3764

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Stark, M., Assum, G. & Krone, W. Single-cell PCR performed with neurofibroma Schwann cells reveals the presence of both alleles of the neurofibromatosis type 1 (NF1) gene. Hum Genet 96, 619–623 (1995). https://doi.org/10.1007/BF00197423

Download citation

Keywords

  • Polymerase Chain Reaction
  • Internal Medicine
  • Progenitor Cell
  • Metabolic Disease
  • Primary Culture