Cancer-related gene expression profiles in NF1-associated pilocytic astrocytomas

Background: individuals affected with neurofibromatosis 1 (NF1) develop juv enile pilocytic astrocytomas (JPA) at an increased frequency, suggesting th at the NF1 gene product, neurofibromin, functions as a negative growth regu lator for astrocytes. Previously, the authors demonstrated that NF1-associa ted astrocytomas exhibit deletions and loss of NF1 gene expression on the D NA and protein levels. However, Little is known about additional genetic ev ents in clinically and radiographically progressive NF1-associated pilocyti c astrocytomas. Objective/methods: To understand the potential role of coop erating genetic events in the development of these low-grade tumors, the au thors used immunohistochemistry and selected confirmatory Western blots to examine nine symptomatic NF1-associated pilocytic astrocytomas for gene pro ducts whose expression patterns are altered in fibrillary astrocytomas. Res ults: 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-R alpha) pro tein expression profiles are not altered in NF1-associated pilocytic astroc ytomas. Similar to their sporadic counterparts, NF1-associated JPA also str ongly expressed PENS, a marker of post-O2A stage oligodendroglial precursor cells. Conclusions: These results suggest that NF1-associated pilocytic as trocytomas lack the genetic changes typically associated with the more clin ically aggressive fibrillary astrocytomas and lay the foundation for future studies to identify NF1 JPA-specific alterations.