RGD Reference Report - IGFBP2 expression predicts IDH-mutant glioma patient survival. - Rat Genome Database

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IGFBP2 expression predicts IDH-mutant glioma patient survival.

Authors: Huang, Lin Eric  Cohen, Adam L  Colman, Howard  Jensen, Randy L  Fults, Daniel W  Couldwell, William T 
Citation: Huang LE, etal., Oncotarget. 2017 Jan 3;8(1):191-202. doi: 10.18632/oncotarget.13329.
RGD ID: 13702476
Pubmed: PMID:27852048   (View Abstract at PubMed)
PMCID: PMC5352106   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.13329   (Journal Full-text)

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.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
ARAFHumanhigh grade glioma disease_progressionIEP  RGD 
ArafRathigh grade glioma disease_progressionISOARAF (Homo sapiens) RGD 
ArafMousehigh grade glioma disease_progressionISOARAF (Homo sapiens) RGD 


Genes (Rattus norvegicus)
Araf  (A-Raf proto-oncogene, serine/threonine kinase)

Genes (Mus musculus)
Araf  (Araf proto-oncogene, serine/threonine kinase)

Genes (Homo sapiens)
ARAF  (A-Raf proto-oncogene, serine/threonine kinase)