Mutation analysis of IDH1 in paired gliomas revealed IDH1 mutation was not associated with malignant progression but predicted longer survival

PLoS One. 2013 Jun 28;8(6):e67421. doi: 10.1371/journal.pone.0067421. Print 2013.

Abstract

Recurrence and progression to higher grade lesions are characteristic behaviors of gliomas. Though IDH1 mutation frequently occurs and is considered as an early event in gliomagenesis, little is known about its role in the recurrence and progression of gliomas. We therefore analysed IDH1 and IDH2 status at codon 132 of IDH1 and codon 172 of IDH2 by direct sequencing and anti-IDH1-R132H immunohistochemistry in 53 paired samples and their recurrences, including 29 low-grade gliomas, 16 anaplastic gliomas and 8 Glioblastomas. IDH1/IDH2 mutation was detected in 32 primary tumors, with 25 low-grade gliomas and 6 anaplastic gliomas harboring IDH1 mutation and 1 low-grade glioma harboring IDH2 mutation. All of the paired tumors showed consistent IDH1 and IDH2 status. Patients were analyzed according to IDH1 status and tumor-related factors. Malignant progression at recurrence was noted in 22 gliomas and was not associated with IDH1 mutation. Survival analysis revealed patients with IDH1 mutated gliomas had a significantly longer progression-free survival (PFS) and overall survival (OS). In conclusion, this study demonstrated a strong tendency of IDH1/IDH2 status being consistent during progression of glioma. IDH1 mutation was not a predictive marker for malignant progression and it was a potential prognostic marker for gliomas of Chinese patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Astrocytoma / genetics*
  • Astrocytoma / mortality
  • Astrocytoma / pathology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation, Missense
  • Neoplasm Recurrence, Local / genetics*
  • Prognosis
  • Proportional Hazards Models
  • Young Adult

Substances

  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human

Grants and funding

This work was supported by The Project for Science and Technology Commission of Shanghai Municipality Grant (No. 10JC1402200 to L.F.Z.), National Natural Science Foundation of China (81172412 to H.K.N.), Shanghai Talents Development Funds (No. 2011063 to Y.Y.), The Grant from Ministry of Health of China (W2012FZ003 to Z.Y.Q.), Wu Jieping medical foundation for clinical research of special fund project (No. 320.6700.1162 to Y.Y.), The Project for National 985 Engineering of China (No.985III-YFX0102 to Y.M.). Science and Technology Commission of Shanghai Municipality Grant (No. 10JC1402200 to L.F.Z.) had a role in study design; National Natural Science Foundation of China (81172412 to H.K.N.) had a role in experiment, data collection and analysis; Shanghai Talents Development Funds (No. 2011063 to Y.Y.) have a role in decisions to follow up, publish and prepare the manuscript.