| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Short Communications |
From the Departments of Pathology*
and
Neurology,
Washington University School of
Medicine, St. Louis, Missouri
Although plexiform neurofibroma (PN) is thought to represent a benign neoplasm with the potential for malignant transformation (malignant peripheral nerve sheath tumor; MPNST), its neoplastic nature has been difficult to prove due to cellular heterogeneity, which hampers standard molecular genetic analysis. Its mixed composition typically includes Schwann cells, fibroblasts, perineurial-like cells, and mast cells. Although NF1 loss of heterozygosity has been reported in subsets of PNs, it remains uncertain which cell type(s) harbor these alterations. Using a dual-color fluorescence in situ hybridization and immunohistochemistry technique, we studied NF1 gene status in S-100 protein-positive and -negative cell subpopulations in archival paraffin-embedded specimens from seven PNs, two atypical PNs, one cellular/atypical PN, and eight MPNSTs derived from 13 patients, seven of which had neurofibromatosis type 1 (NF1). NF1 loss was detected in four of seven PNs and one atypical PN, with deletions entirely restricted to S-100 protein-immunoreactive Schwann cells. In contrast, all eight MPNSTs harbored NF1 deletions, regardless of S-100 protein expression or NF1 clinical status. Our results suggest that the Schwann cell is the primary neoplastic component in PNs and that S-100 protein-negative cells in MPNST represent dedifferentiated Schwann cells, which harbor NF1 deletions in both NF1-associated and sporadic tumors.
This article has been cited by other articles:
 |
|
 |
|
  S. Schoniger and B. A. Summers Localized, Plexiform, Diffuse, and Other Variants of Neurofibroma in 12 Dogs, 2 Horses, and a Chicken Veterinary Pathology, September 1, 2009; 46(5): 904 - 915. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Y. Zou, K. D. Smith, Q.-S. Zhu, J. Liu, I. E. McCutcheon, J. M. Slopis, F. Meric-Bernstam, Z. Peng, W. G. Bornmann, G. B. Mills, et al. Dual targeting of AKT and mammalian target of rapamycin: A potential therapeutic approach for malignant peripheral nerve sheath tumor Mol. Cancer Ther., May 1, 2009; 8(5): 1157 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Mantripragada, G. Spurlock, L. Kluwe, N. Chuzhanova, R. E. Ferner, I. M. Frayling, J. P. Dumanski, A. Guha, V. Mautner, and M. Upadhyaya High-Resolution DNA Copy Number Profiling of Malignant Peripheral Nerve Sheath Tumors Using Targeted Microarray-Based Comparative Genomic Hybridization Clin. Cancer Res., February 15, 2008; 14(4): 1015 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Worley, M. D. Onken, E. Person, D. Robirds, J. Branson, D. H. Char, A. Perry, and J. W. Harbour Transcriptomic versus Chromosomal Prognostic Markers and Clinical Outcome in Uveal Melanoma Clin. Cancer Res., March 1, 2007; 13(5): 1466 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Miller, F. Rangwala, J. Williams, P. Ackerman, S. Kong, A. G. Jegga, S. Kaiser, B. J. Aronow, S. Frahm, L. Kluwe, et al. Large-scale molecular comparison of human schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues. Cancer Res., March 1, 2006; 66(5): 2584 - 2591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K K Mantripragada, A-C Thuresson, A Piotrowski, T Diaz de Stahl, U Menzel, G Grigelionis, R E Ferner, S Griffiths, L Bolund, V Mautner, et al. Identification of novel deletion breakpoints bordered by segmental duplications in the NF1 locus using high resolution array-CGH J. Med. Genet., January 1, 2006; 43(1): 28 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.F. PARADA, C.-H. KWON, and Y. ZHU Modeling Neurofibromatosis Type 1 Tumors in the Mouse for Therapeutic Intervention Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 173 - 176. [Abstract] [PDF]
|
|
|
|
|
|
A. O. Stemmer-Rachamimov, D. N. Louis, G. P. Nielsen, C. R. Antonescu, A. D. Borowsky, R. T. Bronson, D. K. Burns, P. Cervera, M. E. McLaughlin, G. Reifenberger, et al. Comparative Pathology of Nerve Sheath Tumors in Mouse Models and Humans Cancer Res., May 15, 2004; 64(10): 3718 - 3724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Kaufman, B. S. Heinrich, C. Willett, A. Perry, F. Finseth, R. A. Sobel, and M. MacCollin Somatic Instability of the NF2 Gene in Schwannomatosis Arch Neurol, September 1, 2003; 60(9): 1317 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Foster, C. E. Fuller, A. Perry, and J. W. Harbour Status of the NF1 Tumor Suppressor Locus in Uveal Melanoma Arch Ophthalmol, September 1, 2003; 121(9): 1311 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. H. Huijbregts, K. A. Roth, R. E. Schmidt, and S. L. Carroll Hypertrophic Neuropathies and Malignant Peripheral Nerve Sheath Tumors in Transgenic Mice Overexpressing Glial Growth Factor {beta}3 in Myelinating Schwann Cells J. Neurosci., August 13, 2003; 23(19): 7269 - 7280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. McLaughlin and T. Jacks Progesterone Receptor Expression in Neurofibromas Cancer Res., February 15, 2003; 63(4): 752 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Arbiser, B. Govindarajan, X. Bai, H. Onda, A. Kazlauskas, S. D. Lim, M. B. Amin, and L. Claesson-Welsh Functional Tyrosine Kinase Inhibitor Profiling : A Generally Applicable Method Points to a Novel Role of Platelet-Derived Growth Factor Receptor-{beta} in Tuberous Sclerosis Am. J. Pathol., September 1, 2002; 161(3): 781 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Plexiform neurofibromas in NF1: Toward biologic-based therapy Neurology, May 28, 2002; 58(10): 1461 - 1470.
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
