title: [Analyses of IDH1 mutation and MGMT promoter methylation status for 5 cases of long-term survivors with glioblastoma].
abstract: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with an extremely poor prognosis in spite of multimodal treatment approaches. The median survival time of patients with GBM is 15 months, and only 3-5% of patients survive longer than 36 months. Those patients who survive over 36 months after the initial diagnosis are defined as long-term survivors. In this study, we retrospectively performed clinical and molecular analyses of five long-term survivors of GBM (>36 months) and twenty four GBM patients with poor survival time as control group (<36 months) to identify any prognostic factors that potentially contribute to survival. The O6-methylguanine-DNA methyltransferase (MGMT) gene methylation status was evaluated by performing methylation specific polymerase chain reaction assays. The mutation of isocitrate dehydrogenase 1 and 2 were evaluated by the direct sequencing method. All five cases were primary GBMs and the coexistence of the oligodendroglioma component was checked for each case as GBM with oligodendroglioma component. All five cases showed MGMT promoter methylation (5/5). IDH1 mutation was detected in two of the long-term survivors with oligodendroglioma component (2/5) while no IDH1 mutation was detected in the control group. All patients were treated by gross total removal followed by radiotherapy and various chemotherapies including temozolomide. MGMT promoter methylation and IDH1 mutation might be favorable factors for long-term survival in GBM patients.
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Japan.
authors.forename: Yuuta
authors.initials: Y
authors.lastname: Kamoshima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Motegi
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Terasaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Junichi
authors.initials: J
authors.lastname: Murata
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Houkin
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001932:Brain Neoplasms / Q000401:mortality*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005909:Glioblastoma / Q000401:mortality*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012189:Retrospective Studies; D017741:Survivors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D015415:Biomarkers; D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes