Clinicopathologic Implications of NF1 Gene Alterations in Diffuse Gliomas

2015-05-30 00:01:32

Human Pathology; 30 May 2015; DOI: 10.1016/j.humpath.2015.05.014

M. Adelita VizcaĆ­no, M.D., Smit Shah, B.A., Charles G. Eberhart, M.D., PhD., Fausto J. Rodriguez, M.D.


Recent studies have identified somatic alterations in the gene encoding for neurofibromin (NF1) in a subset of glioblastoma (GBM), usually associated with the mesenchymal molecular subtype. To understand the significance of NF1 genetic alterations in diffuse gliomas in general, we evaluated public databases and tested for NF1 copy number alterations in a cohort using fluorescence in situ hybridization (FISH). NF1 genetic loss (homozygous NF1 deletions or mutations with predicted functional consequences) were present in 30 (of 281) (11%) GBM and 21 (of 286) (7%) lower grade gliomas in the Cancer Geneome Atlas (TCGA) data. Furthermore, NF1 loss was associated with worse overall and disease-specific survival in the lower grade glioma, but not GBM, group in this TCGA cohort. IDH1 or 2 mutations co-existed in lower grade gliomas with NF1 loss (36%) but not in GBM. In our cohort studied by FISH, NF1/17q (n=2) or whole Ch17 (n=3) losses were only identified in the GBM group (5/86 (6%)). Tumors with NF1/Ch17 loss were predominantly adult GBM (4/5), lacked EGFR amplification (0/4), strong p53 immunolabeling (1/5) or IDH1 (R132H) protein expression (0/5), but expressed the mesenchymal marker podoplanin in 4/5. NF1 genetic loss occurs in a subset of diffuse gliomas, and its significance deserves further exploration.

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Key Words

Glioma | Neurofibromatosis | Glioblastoma | FISH | Neurofibromin | NF1