title: Predicting the likelihood of an isocitrate dehydrogenase 1 or 2 mutation in diagnoses of infiltrative glioma.
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.
authors.affiliation: Biostatistics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.V., K.C., M.N.N.); Cancer Research Informatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (I.H., E.B.D.); Department of Neurosurgery, University of Kentucky, Lexington, Kentucky (J.M.); Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky (M.W.); Division of Biomedical Informatics, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (E.B.D.).
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Biostatistics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.V., K.C., M.N.N.); Cancer Research Informatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (I.H., E.B.D.); Department of Neurosurgery, University of Kentucky, Lexington, Kentucky (J.M.); Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky (M.W.); Division of Biomedical Informatics, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (E.B.D.).
authors.forename: Zoya
authors.initials: Z
authors.lastname: Voronovich
authors.affiliation: Biostatistics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.V., K.C., M.N.N.); Cancer Research Informatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (I.H., E.B.D.); Department of Neurosurgery, University of Kentucky, Lexington, Kentucky (J.M.); Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky (M.W.); Division of Biomedical Informatics, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (E.B.D.).
authors.forename: Kenneth
authors.initials: K
authors.lastname: Clark
authors.affiliation: Biostatistics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.V., K.C., M.N.N.); Cancer Research Informatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (I.H., E.B.D.); Department of Neurosurgery, University of Kentucky, Lexington, Kentucky (J.M.); Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky (M.W.); Division of Biomedical Informatics, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (E.B.D.).
authors.forename: Isaac
authors.initials: I
authors.lastname: Hands
authors.affiliation: Biostatistics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.V., K.C., M.N.N.); Cancer Research Informatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (I.H., E.B.D.); Department of Neurosurgery, University of Kentucky, Lexington, Kentucky (J.M.); Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky (M.W.); Division of Biomedical Informatics, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (E.B.D.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mannas
authors.affiliation: Biostatistics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.V., K.C., M.N.N.); Cancer Research Informatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (I.H., E.B.D.); Department of Neurosurgery, University of Kentucky, Lexington, Kentucky (J.M.); Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky (M.W.); Division of Biomedical Informatics, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (E.B.D.).
authors.forename: Meggen
authors.initials: M
authors.lastname: Walsh
authors.affiliation: Biostatistics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.V., K.C., M.N.N.); Cancer Research Informatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (I.H., E.B.D.); Department of Neurosurgery, University of Kentucky, Lexington, Kentucky (J.M.); Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky (M.W.); Division of Biomedical Informatics, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (E.B.D.).
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.affiliation: Biostatistics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.V., K.C., M.N.N.); Cancer Research Informatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (I.H., E.B.D.); Department of Neurosurgery, University of Kentucky, Lexington, Kentucky (J.M.); Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky (M.W.); Division of Biomedical Informatics, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (E.B.D.).
authors.forename: Eric B
authors.initials: EB
authors.lastname: Durbin
authors.affiliation: Biostatistics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.V., K.C., M.N.N.); Cancer Research Informatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (I.H., E.B.D.); Department of Neurosurgery, University of Kentucky, Lexington, Kentucky (J.M.); Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky (M.W.); Division of Biomedical Informatics, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (E.B.D.).
authors.forename: Heidi
authors.initials: H
authors.lastname: Weiss
authors.affiliation: Biostatistics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (L.C., H.W.); Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania (Z.V., K.C., M.N.N.); Cancer Research Informatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, Kentucky (I.H., E.B.D.); Department of Neurosurgery, University of Kentucky, Lexington, Kentucky (J.M.); Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky (M.W.); Division of Biomedical Informatics, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, Kentucky (E.B.D.).
authors.forename: Craig
authors.initials: C
authors.lastname: Horbinski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D011379:Prognosis; D054928:Validation Studies as Topic; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: IDH1; IDH2; glioma