title: Glioblastomas with IDH1/2 mutations have a short clinical history and have a favorable clinical outcome.
abstract: OBJECTIVE
  Glioblastomas with isocitrate dehydrogenase 1/2 mutations comprise a biologically distinct subgroup of glioblastomas. We studied isocitrate dehydrogenase 1/2 mutant glioblastomas at the clinical, molecular and radiological levels to define their clinical features, including the prognostic value of isocitrate dehydrogenase 1/2 mutations compared with isocitrate dehydrogenase 1/2 wild-type glioblastomas.
  
  
  METHODS
  We investigated 128 newly diagnosed glioblastoma patients who were treated at our institute between January 2005 and May 2013. Isocitrate dehydrogenase 1/2 mutation status was determined using pyrosequencing. O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation and 1p/19q co-deletions were also analyzed using pyrosequencing and multiplex ligation-dependent probe amplification, respectively.
  
  
  RESULTS
  Isocitrate dehydrogenase 1/2 mutations were detected in 10 of 128 patients (7.8%). Isocitrate dehydrogenase 1/2 mutations were correlated with a younger age, the presence of an oligodendroglial component and 1p/19q co-deletions and a longer survival time. The interval from initial symptom to initial operation did not differ according to isocitrate dehydrogenase 1/2 mutation status (median interval: 2.3 versus 1.2 months; P = 0.13). Two of three isocitrate dehydrogenase 1/2 mutant glioblastomas harboring 1p/19q co-deletions had an oligodendroglial component and were associated with a prolonged survival time. Multivariate analysis of 90 patients treated with temozolomide-based chemoradiotherapy indicated that age, extent of resection, postoperative Karnofsky performance score and O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation were correlated with better survival. Isocitrate dehydrogenase 1/2 mutations showed a trend for improved survival (P = 0.068).
  
  
  CONCLUSIONS
  Most isocitrate dehydrogenase 1/2 mutant glioblastomas have a short clinical history, and some isocitrate dehydrogenase 1/2 mutant glioblastomas harboring 1p/19q co-deletions behave like oligodendroglial tumors. Isocitrate dehydrogenase 1/2 mutations may have a positive prognostic impact on the Japanese population.
authors.affiliation: Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Chuo-ku.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohno
authors.affiliation: Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Chuo-ku yonarita@ncc.go.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Narita
authors.affiliation: Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Chuo-ku.
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Miyakita
authors.affiliation: Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Chuo-ku.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Chuo-ku Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Osaka.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Arita
authors.affiliation: Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Chuo-ku.
authors.forename: Motoki
authors.initials: M
authors.lastname: Yonezawa
authors.affiliation: Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Chuo-ku.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Chuo-ku Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Chuo-ku.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Chuo-ku.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takami
authors.affiliation: Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Chuo-ku.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ichimura
authors.affiliation: Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Chuo-ku Department of Neurosurgery, Teikyo University School of medicine University Hospital, Mizonokuchi, Kawasaki, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Shibui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D059248:Chemoradiotherapy; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D019175:DNA Methylation; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D007564:Japan; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic; D000077204:Temozolomide
chemical_list: D006147:Guanine; D003606:Dacarbazine; C008449:O-(6)-methylguanine; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D000077204:Temozolomide
keywords: IDH1/2; MGMT; glioblastoma; prognostic factor; temozolomide