title: Prognostic value of isocitrate dehydrogenase 1, O6-methylguanine-DNA methyltransferase promoter methylation, and 1p19q co-deletion in Japanese malignant glioma patients.
abstract: BACKGROUND
  To determine the prognostic value of isocitrate dehydrogenase 1 (IDH1) mutation, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and 1p/19q co-deletion in Japanese patients with malignant gliomas.
  
  
  METHODS
  We studied 267 malignant gliomas, which included 171 glioblastomas (GBMs), 40 anaplastic astrocytomas (AAs), 30 anaplastic oligodendrogliomas (AOs), and 26 anaplastic oligoastrocytomas (AOAs). These malignant gliomas were divided into 2 groups (Group 1: GBM + AA, Group 2: AO + AOA) according to the presence of the oligodendroglioma component. We examined IDH1 mutation and MGMT promoter methylation in each group by direct sequencing and methylation-specific PCR, respectively. We further examined 1p/19q co-deletion in Group 2 by fluorescence in situ hybridization. Survival between groups was compared by Kaplan-Meier analysis.
  
  
  RESULTS
  In Group 1, patients with IDH1 mutations exhibited a significantly longer survival time than patients with wild-type IDH1. However, no significant difference was observed in Group 2, although patients with IDH1 mutations tended to show prolonged survival. For both Group 1 and Group 2, patients with MGMT methylation survived longer than those without this methylation. Further, patients with 1p/19q co-deletion showed significantly better outcome in Group 2.
  
  
  CONCLUSIONS
  Our study confirms the utility of IDH1 mutations and MGMT methylation in predicting the prognosis of Group 1 patients (GBM + AA) and demonstrated that IDH1 mutations may serve as a more reliable prognostic factor for such patients. We also showed that MGMT methylation and 1p/19q co-deletion rather than IDH1 mutations were prognostic factors for Group 2 patients (AOA + AO). Our study suggests that patients survive longer if they have IDH1 mutations and undergo total resection. Further, irrespective of MGMT promoter methylation status, the prognosis of glioma patients can be improved if total resection is performed. Moreover, our study includes the largest number of Japanese patients with malignant gliomas that has been analyzed for these three markers. We believe that our findings will increase the awareness of oncologists in Japan of the value of these markers for predicting prognosis and designing appropriate therapeutic strategies for treating this highly fatal disease.
authors.affiliation: Department of Neurosurgery, Graduate School of Medical Science, Kumamoto University, 7-5, Inada, Obihiro, Hokkaido 080-0039, Japan. yosinobu@hokuto7.or.jp.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakamura
authors.forename: Keishi
authors.initials: K
authors.lastname: Makino
authors.forename: Takuichiro
authors.initials: T
authors.lastname: Hide
authors.forename: Daisuke
authors.initials: D
authors.lastname: Muta
authors.forename: Hajime
authors.initials: H
authors.lastname: Kamada
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kuratsu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes