title: Is the absolute value of O(6)-methylguanine-DNA methyltransferase gene messenger RNA a prognostic factor, and does it predict the results of treatment of glioblastoma with temozolomide?
abstract: OBJECTIVE
  Methylation of O(6)-methylguanine-DNA methyltransferase (MGMT) has been reported to be a good prognostic factor for patients with glioblastoma multiforme (GBM). To determine whether the absolute value of MGMT messenger RNA (mRNA) might be a prognostic factor and useful for predicting the therapeutic effectiveness of temozolomide, especially with regard to GBMs, the authors measured the absolute value of MGMT mRNA in gliomas by using real-time reverse-transcription polymerase chain reaction (RT-PCR).
  
  
  METHODS
  MGMT mRNA was measured in 140 newly diagnosed gliomas by real-time RT-PCR using the Taq-Man probe. Among 73 GBMs, 45 had been initially treated with temozolomide and radiation.
  
  
  RESULTS
  The mean MGMT mRNA value was significantly lower in oligodendroglial tumors than in other tumors. In the 73 GBMs, a significant prognostic factor for progression-free survival was fewer than 1000 copies/ μgRNA of MGMT mRNA (p = 0.0150). Of 45 patients with GBMs that had been treated with temozolomide and radiation, progression-free survival was significantly longer for those whose GMB had fewer than 1000 copies/μgRNA of MGMT mRNA than for those whose GBM had more than 1000 copies/μgRNA (p = 0.0090). In 32 patients with GBMs treated by temozolomide and radiation whose age was younger than 75 years and whose Karnofsky Performance Scale score was more than 70, progression-free and overall survival times were longer for those with GBMs of fewer than 5000 copies/μgRNA of MGMT mRNA than for those with GBMs of more than 5000 copies/μgRNA (p = 0.0365 and p = 0.0312).
  
  
  CONCLUSIONS
  MGMT mRNA might be useful as a prognostic factor and for predicting the results of therapy for GBMs treated by temozolomide. New individual adjuvant therapy based on the results of MGMT mRNA quantitation has been proposed.
authors.affiliation: Department of Neuro-Oncology and Neurosurgery, Tokyo Nishi Tokushukai Hospital;
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Jiro
authors.initials: J
authors.lastname: Akimoto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Narita
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Oka
authors.forename: Takashi
authors.initials: T
authors.lastname: Tashiro
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D012333:RNA, Messenger; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide
keywords: ACNU = 1-(4-amino-2-methyl-5-pyrimidynyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride; G-CIMP = glioma-CpG island methylator phenotype; GADPH = glyceraldehyde-3-phosphate dehydrogenase; GBM = glioblastoma multiforme; MGMT; MGMT = O6-methylguanine-DNA methyltransferase; RT-PCR = reverse-transcription polymerase chain reaction; cDNA = complementary DNA; glioblastoma; mRNA; mRNA = messenger RNA; oncology; real-time RT-PCR; temozolomide