Predicting the likelihood of an isocitrate dehydrogenase 1 or 2 mutation in diagnoses of infiltrative glioma

Neuro Oncol. 2014 Nov;16(11):1478-83. doi: 10.1093/neuonc/nou097. Epub 2014 May 23.

Abstract

Background: Several variables are associated with the likelihood of isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation in gliomas, though no guidelines yet exist for when testing is warranted, especially when an R132H IDH1 immunostain is negative.

Methods: A cohort of 89 patients was used to build IDH1/2 mutation prediction models in World Health Organization grades II-IV gliomas, and an external cohort of 100 patients was used for validation. Logistic regression and backward model selection with the Akaike information criterion were used to develop prediction models.

Results: A multivariable model, incorporating patient age, glioblastoma multiforme diagnosis, and prior history of grade II or III glioma, was developed to predict IDH1/2 mutation probability. This model generated an area under the curve (AUC) of 0.934 (95% CI: 0.878, 0.978) in the external validation cohort and 0.941 (95% CI: 0.918, 0.962) in the cohort of The Cancer Genome Atlas. When R132H IDH1 immunostain information was added, AUC increased to 0.986 (95% CI: 0.967, 0.998). This model had an AUC of 0.947 (95% CI: 0.891, 0.995) in predicting whether an R132H IDH1 immunonegative case harbored a less common IDH1 or IDH2 mutation. The models were also 94% accurate in predicting IDH1/2 mutation status in gliomas from The Cancer Genome Atlas. An interactive web-based application for calculating the probability of an IDH1/2 mutation is now available using these models.

Conclusions: We have integrated multiple variables to generate a probability of an IDH1/2 mutation. The associated web-based application can help triage diffuse gliomas that would benefit from mutation testing in both clinical and research settings.

Keywords: IDH1; IDH2; glioma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Glioma / diagnosis*
  • Glioma / genetics
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Models, Statistical*
  • Mutation / genetics*
  • Neoplasm Grading
  • Prognosis
  • Validation Studies as Topic
  • Young Adult

Substances

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