Phenotypic Variations in NF1-Associated Low Grade Gliomas: Possible Role for Increased mTOR Activation in a Subset.
Mark Jentoft, Caterina Giannini, Ling Cen, Bernd W Scheithauer, Bridget Hoesley, Jann N Sarkaria, Patrice C Abell-Aleff, Ying Li, Fausto J Rodriguez. Mayo Clinic, Rochester, MN
Background: Low grade gliomas are the predominant tumors arising in the central nervous system in neurofibromatosis type 1(NF1) patients. Although most of these represent pilocytic astrocytomas (PA) a subset are difficult to classify, and have been termed “low grade astrocytoma subtype indeterminate” (LGSI). Some of these tumors have peculiar morphology, including plump cytoplasmic processes and macronucleoli.
Design: In the current study we performed electron microscopy, followed by gene expression, immunohistochemical and western blot analyses to identify biological differences underlying phenotypic variation in NF1-associated low grade glioma.
Results: Electron microscopy demonstrated glial intermediate filaments and frequent Rosenthal fiber material in both PA and LGSI. However, in addition dense core granules and/or aligned microtubules were found most frequently in the LGSI group only (2/3 cases), compared to the PA group (1/10 cases). Analysis of global gene expression data obtained using Affymetrix HG-U133 Plus2.0 chips (1 LGSI, 5 PA), and western blot analysis for pS6 (1 LGSI, 2 PA) demonstrated a gene expression profile reflecting neuronal differentiation and increased pS6 levels consistent with mTOR activation in the LGSI compared with PA. These findings were confirmed by immunohistochemistry for diagnostic neuronal markers, as well as combined pS6/pS6 kinase staining in 4/4 LGSI and 5/13 PA in formalin fixed paraffin embedded tissues (p=0.02).
Conclusions: Phenotypic variations in NF1-associated low grade glioma may be reflected in differential expression of neuronal-related genes and increased mTOR activation.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 225, Tuesday Afternoon