title: Prognostic value of MGMT promoter methylation and TP53 mutation in glioblastomas depends on IDH1 mutation.
abstract: Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas. We investigated the prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.
authors.affiliation: Department of Neuroradiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China E-mail : djpbeijing@hotmail.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Yin-Yan
authors.initials: YY
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Jiang-Fei
authors.initials: JF
authors.lastname: Wang
authors.forename: Shao-Wu
authors.initials: SW
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Dai
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes