IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas

J Neurooncol. 2012 Jul;108(3):403-10. doi: 10.1007/s11060-012-0844-1. Epub 2012 Mar 13.

Abstract

This study investigated the prognostic and predictive significance of IDH1 and IDH2 mutations in low-grade astrocytomas (LGA). The presence and consistency of IDH mutations during the progression of LGA to secondary high-grade gliomas (sHGG) were detected. Samples of patients with LGA and sHGG were investigated. The genomic regions around IDH1 codon 132 and IDH2 codon 172 were PCR amplified and directly sequenced. Furthermore, the MGMT promoter status was provided using the methylation-specific PCR. Our population comprised 71 patients with a total of 45 pairs of LGA and their consecutive sHGG. Median follow-up was 9.6 years. IDH mutations were found in 36/45 LGA (80%) and their sHGG without changes in the mutation status. A total of 71 patients with LGA were analyzed according to clinical and molecular tumor-related factors: 56/71 patients (78.8%) had an IDH mutation without significant influence on the progression-free or overall survival (OS), and 22/71 (31%) of the patients received postoperative radiotherapy (RT) after diagnosis of LGA. Patients with early RT but without IDH mutations had the shortest survival. Our study shows that IDH mutation status is stable during the progression course of LGA to sHGG. The presence of IDH mutations fails to demonstrate a significant influence on survival in the multivariate analysis of LGA patients. Early RT appears to be beneficial only LGA patients with IDH-mutations.

MeSH terms

  • Adult
  • Aged
  • Astrocytoma / genetics*
  • Astrocytoma / mortality
  • Astrocytoma / therapy
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy
  • Combined Modality Therapy
  • DNA Methylation
  • DNA, Neoplasm / genetics
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glioma / genetics*
  • Glioma / mortality
  • Glioma / therapy
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Grading
  • Polymerase Chain Reaction
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Survival Rate
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Isocitrate Dehydrogenase
  • isocitrate dehydrogenase 2, human
  • IDH1 protein, human