Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.41 (isocitrate dehydrogenase)
 3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations of the isocitrate dehydrogenase (IDH) 1 and 2 genes occur in ~80% of lower-grade (WHO grade II and grade III) gliomas. Mutant IDH produces (R)-2-hydroxyglutarate, which induces DNA hypermethylation and presumably drives tumorigenesis. Interestingly, IDH mutations are associated with improved survival in glioma patients, but the underlying mechanism for the difference in survival remains unclear. Through comparative analyses of 286 cases of IDH-wildtype and IDH-mutant lower-grade glioma from a TCGA data set, we report that IDH-mutant gliomas have increased expression of tumor-suppressor genes (NF1, PTEN, and PIK3R1) and decreased expression of oncogenes(AKT2, ARAF, ERBB2, FGFR3, and PDGFRB) and glioma progression genes (FOXM1, IGFBP2, and WWTR1) compared with IDH-wildtype gliomas. Furthermore, each of these genes is prognostic in overall gliomas; however, within the IDH-mutant group, none remains prognostic except IGFBP2 (encodinginsulin-like growth factor binding protein 2). Through validation in an independent cohort, we show that patients with low IGFBP2 expressiondisplay a clear advantage in overall and disease-free survival, whereas those with high IGFBP2 expressionhave worse median survival than IDH-wildtype patients. These observations hold true across different histological and molecular subtypes of lower-grade glioma. We propose therefore that an unexpected biological consequence of IDH mutations in glioma is to ameliorate patient survival by promoting tumor-suppressor signaling while inhibiting that of oncogenes, particularly IGFBP2.
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PMID:IGFBP2 expression predicts IDH-mutant glioma patient survival. 2785 48

Glioblastoma is the most common malignant brain tumor in adults. Unfortunately, it has a very poor prognosis and no cure. In a recent paper by Yuan et al. (Bioscience Reports (2019), DOI:10.1042/BSR20190045) RNAscope was used to detect insulin-like growth factor binding protein 2 (IGFBP2) mRNA in glioblastoma biopsies. The study revealed that patients with high levels of IGFBP2 mRNA had shorter survival and that IGFBP2 transcript level was an independent prognostic factor. It is also of value to determine the prognostic effect of IGFBP2 on established biomarkers such as isocitrate dehydrogenase (IDH1) mutations or telomerase reverse transcriptase (TERT) promoter mutation. In the present study, the combination of having a TERT promoter mutation, and at the same time a high level of IGFBP2 mRNA, was associated with very poor survival rates. It was concluded that IGFBP2 predicts the survival of the patients with TERT promoter mutation. This finding may have important implications for glioblastoma prognosis. IGFBP2 re-emerges as a candidate biomarker and potential therapeutic target in glioma. Further research into its functional roles during glioma progression may provide additional insights into this deadly disease.
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PMID:Expanding the scope of candidate prognostic marker IGFBP2 in glioblastoma. 3113 64