title: IDH1/IDH2 mutations define the prognosis and molecular profiles of patients with gliomas: a meta-analysis.
abstract: BACKGROUND
  Isocitrate dehydrogenase isoforms 1 and 2 (IDH1 and IDH2) mutations have received considerable attention since the discovery of their relation with human gliomas. The predictive value of IDH1 and IDH2 mutations in gliomas remains controversial. Here, we present the results of a meta-analysis of the associations between IDH mutations and both progression-free survival (PFS) and overall survival (OS) in gliomas. The interrelationship between the IDH mutations and MGMT promoter hypermethylation, EGFR amplification, codeletion of chromosomes 1p/19q and TP53 gene mutation were also revealed.
  
  
  RESULTS
  An electronic literature search of public databases (PubMed, Embase databases) was performed. In total, 10 articles, including 12 studies in English, with 2,190 total cases were included in the meta-analysis. The IDH mutations were frequent in WHO grade II and III glioma (59.5%) and secondary glioblastomas (63.4%) and were less frequent in primary glioblastomas (7.13%). Our study provides evidence that IDH mutations are tightly associated with MGMT promoter hypermethylation (P<0.001), 1p/19q codeletion (P<0.001) and TP53 gene mutation (P<0.001) but are mutually exclusive with EGFR amplification (P<0.001). This meta-analysis showed that the combined hazard ratio (HR) estimate for overall survival and progression-free survival in patients with IDH mutations was 0.33 (95% CI: 0.25-0.42) and 0.38 (95% CI: 0.21-0.68), compared with glioma patients whose tumours harboured the wild-type IDH. Subgroup analyses based on tumour grade also revealed that the presence of IDH mutations was associated with a better outcome.
  
  
  CONCLUSIONS
  Our study suggests that IDH mutations, which are closely linked to the genomic profile of gliomas, are potential prognostic biomarkers for gliomas.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.forename: Haitao
authors.initials: H
authors.lastname: Xu
authors.forename: Pin
authors.initials: P
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Yan
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Aihua
authors.initials: A
authors.lastname: Gu
mesh_terms: D005910:Glioma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D009154:Mutation; D060787:Neoplasm Grading; D011379:Prognosis
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
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