Neurology 2001;56:885-890
© 2001 American Academy of Neurology
Articles
Cancer-related gene expression profiles in NF1-associated pilocytic astrocytomas
Jun Li, MD, PhD;,
Arie Perry, MD;,
C. David James, PhD; and
David H. Gutmann, MD, PhD
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.
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