IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas

Neurology. 2010 Oct 26;75(17):1560-6. doi: 10.1212/WNL.0b013e3181f96282.

Abstract

Objectives: Recent studies have shown that IDH1 and IDH2 mutations occur frequently in gliomas, including low-grade gliomas. However, their impact on the prognosis and chemosensitivity of low-grade gliomas remains unclear.

Methods: Search for IDH1 and IDH2 mutations, loss of heterozygosity on chromosomes 1p and 19q, MGMT promoter methylation, and p53 expression was performed in a series of 271 low-grade gliomas and correlated with overall survival. A subgroup of 84 patients treated up-front with temozolomide was individualized. Response to temozolomide was evaluated by progression-free survival, as well as by tumor size on successive MRI scans, and then correlated with molecular alterations.

Results: IDH (IDH1 or IDH2) mutations were found in 132/189 patients (70%). IDH mutation and 1p-19q codeletion were associated with prolonged overall survival in univariate (p = 0.002 and p = 0.0001) and multivariate analysis (p = 0.003 and p = 0.004). 1p-19q codeletion, MGMT promoter methylation, and IDH mutation (p = 0.01) were correlated with a higher rate of response to temozolomide. Further analysis of the course of the disease prior to any treatment except for surgery (untreated subgroup) showed that 1p-19q codeletion was associated with prolonged progression-free survival in univariate analysis, whereas IDH mutation was not.

Conclusion: IDH mutation appears to be a significant marker of positive prognosis and chemosensitivity in low-grade gliomas, independently of 1p-19q codeletion, whereas its impact on the course of untreated tumors seems to be limited.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / mortality
  • Chi-Square Distribution
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • DNA Modification Methylases / genetics
  • DNA Mutational Analysis
  • DNA Repair Enzymes / genetics
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Disease-Free Survival
  • Female
  • Glioma* / drug therapy
  • Glioma* / genetics
  • Glioma* / mortality
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Loss of Heterozygosity / genetics
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Pharmacogenetics*
  • Predictive Value of Tests
  • Retrospective Studies
  • Statistics as Topic
  • Temozolomide
  • Tumor Suppressor Proteins / genetics
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Tumor Suppressor Proteins
  • Dacarbazine
  • IDH2, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide