title: Analysis of IDH1 and IDH2 mutations in Japanese glioma patients.
abstract: A recent study reported on mutations in the active site of the isocitrate dehydrogenase 1 (IDH1) gene in several types of gliomas. All mutations detected resulted in an amino acid exchange at position 132. We analyzed the genomic region spanning wild-type R132 of IDH1 by direct sequencing in 125 glial tumors. A total of 39 IDH1 mutations were observed. Mutations of the IDH2 gene, homologous to IDH1, were often detected in gliomas without IDH1 mutations. In the present study, R172 mutation of the IDH2 gene was detected in one anaplastic astrocytoma. IDH1 or IDH2 mutations were frequently in oligodendrogliomas (67%), anaplastic astrocytomas (62%), anaplastic oligoastrocytomas (75%), anaplastic oligodendrogliomas (50%), secondary glioblastomas (67%), gangliogliomas (38%), and anaplastic gangliogliomas (60%). Primary glioblastomas were characterized by a low frequency of mutations (5%) at amino acid position 132 of IDH1. Mutations of the IDH1 or IDH2 genes were significantly associated with improved outcome in patients with anaplastic astrocytomas. Our data suggest that IDH1 or IDH2 mutation plays a role in early tumor progression of several types of glioma and might arise from a common glial precursor. The infrequency of IDH1 mutation in primary glioblastomas revealed that these subtypes are genetically distinct entities from other glial tumors.
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. sono@nsg.med.tohoku.ac.jp
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sonoda
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kumabe
authors.forename: Taigen
authors.initials: T
authors.lastname: Nakamura
authors.forename: Ryuta
authors.initials: R
authors.lastname: Saito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kanamori
authors.forename: Yoji
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
mesh_terms: D000328:Adult; D044466:Asian People; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human