Nuclear IMPDH Filaments in Human Gliomas
| Autor: | Long Cheng, David G. Munoz, John Woulfe, Narges Ahangari, Josée Coulombe, Elizabeth C. Engle, Douglas A. Gray |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Proliferation index
Pathology and Forensic Medicine Cohort Studies Mice Cellular and Molecular Neuroscience IMP Dehydrogenase Antigen Tubulin IMP dehydrogenase Glioma medicine Animals Humans Cell Nucleus Mice Knockout biology Brain Neoplasms Chemistry Original Articles General Medicine medicine.disease Molecular biology Cell nucleus medicine.anatomical_structure Neurology biology.protein sense organs Neurology (clinical) Antibody Nucleus Lamin |
| Zdroj: | J Neuropathol Exp Neurol |
| ISSN: | 1554-6578 0022-3069 |
| DOI: | 10.1093/jnen/nlab090 |
| Popis: | The analysis of nuclear morphology plays an important role in glioma diagnosis and grading. We previously described intranuclear rods (rods) labeled with the SDL.3D10 monoclonal antibody against class III beta-tubulin (TUBB3) in human ependymomas. In a cohort of adult diffuse gliomas, we identified nuclear rods in 71.1% of IDH mutant lower-grade gliomas and 13.7% of IDH wild-type glioblastomas (GBMs). The presence of nuclear rods was associated with significantly longer postoperative survival in younger (≤65) GBM patients. Consistent with this, nuclear rods were mutually exclusive with Ki67 staining and their prevalence in cell nuclei inversely correlated with the Ki67 proliferation index. In addition, rod-containing nuclei showed a relative depletion of lamin B1, suggesting a possible association with senescence. To gain insight into their functional significance, we addressed their antigenic properties. Using a TUBB3-null mouse model, we demonstrate that the SDL.3D10 antibody does not bind TUBB3 in rods but recognizes an unknown antigen. In the present study, we show that rods show immunoreactivity for the nucleotide synthesizing enzymes inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase. By analogy with the IMPDH filaments that have been described previously, we postulate that rods regulate the activity of nucleotide-synthesizing enzymes in the nucleus by sequestration, with important implications for glioma behavior. |
| Databáze: | OpenAIRE |
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