Cancer-related gene expression profiles in NF1-associated pilocytic astrocytomas.
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
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 alpha (PDGF-Ralpha) 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.
Li
J
J
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Perry
A
A
James
C D
CD
Gutmann
D H
DH
D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000150:complications* / Q000473:pathology*; D001932:Brain Neoplasms / Q000150:complications* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009456:Neurofibromatosis 1 / Q000150:complications* / Q000473:pathology*