| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Departments of Neurology (Drs. Li and Gutmann) and Neuropathology (Dr. Perry), Washington University School of Medicine, St. Louis, MO; and the Division of Experimental Pathology (Dr. James), the Mayo Clinic and Foundation, Rochester, MN.
Address correspondence and reprint requests to Dr. David H. Gutmann, Department of Neurology, Washington University School of Medicine, Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, e-mail: gutmannd{at}neuro.wustl.edu
BACKGROUND: Individuals affected with neurofibromatosis 1 (NF1) develop juvenile pilocytic astrocytomas (JPA) at an increased frequency, suggesting that the NF1 gene product, neurofibromin, functions as a negative growth regulator for astrocytes. Previously, the authors demonstrated that NF1-associated astrocytomas exhibit deletions and loss of NF1 gene expression on the DNA and protein levels. However, little is known about additional genetic events in clinically and radiographically progressive NF1-associated pilocytic astrocytomas.
OBJECTIVE/METHODS: To understand the potential role of cooperating genetic events in the development of these low-grade tumors, the authors used immunohistochemistry and selected confirmatory Western blots to examine nine symptomatic NF1-associated pilocytic astrocytomas for gene products whose expression patterns are altered in fibrillary astrocytomas.
RESULTS: The authors demonstrate that p53, p16, retinoblastoma (RB), epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), platelet-derived growth factor A (PDGF-A) and PDGF receptor 
(PDGF-R) protein expression profiles are not altered in NF1-associated pilocytic astrocytomas. Similar to their sporadic counterparts, NF1-associated JPA also strongly expressed PEN5, a marker of post-O2A stage oligodendroglial precursor cells.
CONCLUSIONS: These results suggest that NF1-associated pilocytic astrocytomas lack the genetic changes typically associated with the more clinically aggressive fibrillary astrocytomas and lay the foundation for future studies to identify NF1 JPA-specific alterations.
This article has been cited by other articles:
|
|
 |
|
  C F Parsa and S Givrad Pilocytic astrocytomas as hamartomas: implications for treatment Br J Ophthalmol, January 1, 2008; 92(1): 3 - 6. [Full Text] [PDF]
|
|
|
|
|
|
C F Parsa and S Givrad Juvenile pilocytic astrocytomas do not undergo spontaneous malignant transformation: grounds for designation as hamartomas Br J Ophthalmol, January 1, 2008; 92(1): 40 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhu, T. Harada, L. Liu, M. E. Lush, F. Guignard, C. Harada, D. K. Burns, M. L. Bajenaru, D. H. Gutmann, and L. F. Parada Inactivation of NF1 in CNS causes increased glial progenitor proliferation and optic glioma formation Development, December 15, 2005; 132(24): 5577 - 5588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Sharma, B. A. Zehnbauer, M. A. Watson, and D. H. Gutmann RAS pathway activation and an oncogenic RAS mutation in sporadic pilocytic astrocytoma Neurology, October 25, 2005; 65(8): 1335 - 1336. [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Bajenaru, M. R. Hernandez, A. Perry, Y. Zhu, L. F. Parada, J. R. Garbow, and D. H. Gutmann Optic Nerve Glioma in Mice Requires Astrocyte Nf1 Gene Inactivation and Nf1 Brain Heterozygosity Cancer Res., December 15, 2003; 63(24): 8573 - 8577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Gutmann, C. D. James, M. Poyhonen, D. N. Louis, R. Ferner, A. Guha, S. Hariharan, D. Viskochil, and A. Perry Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1 Neurology, November 25, 2003; 61(10): 1397 - 1400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Tada, M. Kochi, H. Saya, J.-i. Kuratsu, S. Shiraishi, T. Kamiryo, N. Shinojima, and Y. Ushio Preliminary observations on genetic alterations in pilocytic astrocytomas associated with neurofibromatosis 1 Neuro-oncol, October 1, 2003; 5(4): 228 - 234. [Abstract] [PDF]
|
|
|
|
 |
|
 M. R. Bennett, T. A. Rizvi, S. Karyala, R. D. McKinnon, and N. Ratner Aberrant Growth and Differentiation of Oligodendrocyte Progenitors in Neurofibromatosis Type 1 Mutants J. Neurosci., August 6, 2003; 23(18): 7207 - 7217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-y. Huang, Y. Wu, S. P. Burke, and D. H. Gutmann The 43,000 Growth-associated Protein Functions as a Negative Growth Regulator in Glioma Cancer Res., June 1, 2003; 63(11): 2933 - 2939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Gutmann Review Article : Neurofibromin in the Brain J Child Neurol, August 1, 2002; 17(8): 592 - 601. [Abstract] [PDF]
|
|
|
|
 |
|
 M. L. Bajenaru, Y. Zhu, N. M. Hedrick, J. Donahoe, L. F. Parada, and D. H. Gutmann Astrocyte-Specific Inactivation of the Neurofibromatosis 1 Gene (NF1) Is Insufficient for Astrocytoma Formation Mol. Cell. Biol., July 15, 2002; 22(14): 5100 - 5113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Gutmann, N. M. Hedrick, J. Li, R. Nagarajan, A. Perry, and M. A. Watson Comparative Gene Expression Profile Analysis of Neurofibromatosis 1-associated and Sporadic Pilocytic Astrocytomas Cancer Res., April 1, 2002; 62(7): 2085 - 2091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ruggieri and R. J. Packer Why do benign astrocytomas become malignant in NF1? Neurology, April 10, 2001; 56(7): 827 - 827. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
