IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas

Clin Cancer Res. 2009 Oct 1;15(19):6002-7. doi: 10.1158/1078-0432.CCR-09-0715. Epub 2009 Sep 15.


Purpose: To establish the frequency of IDH1 mutations in glioblastomas at a population level, and to assess whether they allow reliable discrimination between primary (de novo) glioblastomas and secondary glioblastomas that progressed from low-grade or anaplastic astrocytoma.

Experimental design: We screened glioblastomas from a population-based study for IDH1 mutations and correlated them with clinical data and other genetic alterations.

Results: IDH1 mutations were detected in 36 of 407 glioblastomas (8.8%). Glioblastoma patients with IDH1 mutations were younger (mean, 47.9 years) than those with EGFR amplification (60.9 years) and were associated with significantly longer survival (mean, 27.1 versus 11.3 months; P < 0.0001). IDH1 mutations were frequent in glioblastomas diagnosed as secondary (22 of 30; 73%), but rare in primary glioblastomas (14 of 377; 3.7%: P < 0.0001). IDH1 mutations as genetic marker of secondary glioblastoma corresponded to the respective clinical diagnosis in 95% of cases. Glioblastomas with IDH1 mutation diagnosed as primary had clinical and genetic profiles similar to those of secondary glioblastomas, suggesting that they may have rapidly progressed from a less malignant precursor lesion that escaped clinical diagnosis and were thus misclassified as primary. Conversely, glioblastomas without IDH1 mutations clinically diagnosed as secondary typically developed from anaplastic rather than low-grade gliomas, suggesting that at least some were actually primary glioblastomas, that may have been misclassified, possibly due to histologic sampling error.

Conclusion: IDH1 mutations are a strong predictor of a more favorable prognosis and a highly selective molecular marker of secondary glioblastomas that complements clinical criteria for distinguishing them from primary glioblastomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Astrocytoma / diagnosis
  • Astrocytoma / genetics
  • Astrocytoma / mortality
  • Astrocytoma / pathology*
  • Base Sequence
  • Biomarkers, Tumor / genetics
  • DNA Mutational Analysis
  • Female
  • Gene Expression Profiling
  • Glioblastoma / diagnosis*
  • Glioblastoma / genetics
  • Glioblastoma / secondary*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Mutation / physiology
  • Nervous System Neoplasms / diagnosis
  • Nervous System Neoplasms / genetics
  • Nervous System Neoplasms / mortality
  • Nervous System Neoplasms / pathology*
  • Prognosis
  • Survival Analysis


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