IDH-1R132H mutation status in diffuse glioma patients: implications for classification

Oncotarget. 2016 May 24;7(21):31393-400. doi: 10.18632/oncotarget.8918.

Abstract

WHO2007 grading of diffuse gliomas in adults is well-established. However, IDH mutations make classification of gliomas according to the WHO2007 edition controversial. Here, we characterized IDH-1R132H mut status in a cohort of 670 adult patients with different WHO2007 grades of diffuse glioma. Patient characteristics, clinical data and prognoses were obtained from medical records. Patients with IDH-1R132H mut were younger and had better clinical outcomes than those without mutations. Differences in age among patients with astrocytomas of different WHO2007 grades were eliminated after patients were grouped based on IDH-1R132H status. IDH-1R132H mut was present more often in patients with lower Ki-67 and MGMT protein levels and higher mutant p53 levels. Ki-67 was also strongly associated with WHO2007 grade independently of IDH-1R132H mut status. Moreover, patients with Ki-67<30 survived longer than those with Ki-67≥30, regardless of IDH-1R132H mut status. Patients in the IDH-1R132H mut group with lower MGMT protein levels also had better clinical outcomes than those in other groups. Our results indicate that to better treat gliomas, IDH mutation status should be included when determining WHO2007 grade in glioma patients.

Keywords: IDH-1R132H mutation; Ki-67; gliomas; molecular pathology; prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / classification
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Cohort Studies
  • Female
  • Glioma / classification
  • Glioma / genetics*
  • Glioma / metabolism
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Neoplasm Grading
  • Prognosis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Isocitrate Dehydrogenase
  • IDH1 protein, human