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Author (up) Arita, H.; Yamasaki, K.; Matsushita, Y.; Nakamura, T.; Shimokawa, A.; Takami, H.; Tanaka, S.; Mukasa, A.; Shirahata, M.; Shimizu, S.; Suzuki, K.; Saito, K.; Kobayashi, K.; Higuchi, F.; Uzuka, T.; Otani, R.; Tamura, K.; Sumita, K.; Ohno, M.; Miyakita, Y.; Kagawa, N.; Hashimoto, N.; Hatae, R.; Yoshimoto, K.; Shinojima, N.; Nakamura, H.; Kanemura, Y.; Okita, Y.; Kinoshita, M.; Ishibashi, K.; Shofuda, T.; Kodama, Y.; Mori, K.; Tomogane, Y.; Fukai, J.; Fujita, K.; Terakawa, Y.; Tsuyuguchi, N.; Moriuchi, S.; Nonaka, M.; Suzuki, H.; Shibuya, M.; Maehara, T.; Saito, N.; Nagane, M.; Kawahara, N.; Ueki, K.; Yoshimine, T.; Miyaoka, E.; Nishikawa, R.; Komori, T.; Narita, Y.; Ichimura, K. url  doi
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  Title A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas Type Journal Article
  Year 2016 Publication Acta Neuropathologica Communications Abbreviated Journal Acta Neuropathol Commun  
  Volume 4 Issue 1 Pages 79  
  Keywords 1p19q; Glioblastoma; Glioma; Idh1/2; Molecular classification; Prognostic factor; Tert; Temozolomide  
  Abstract The prognostic impact of TERT mutations has been controversial in IDH-wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGMT methylation status or patients' treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT promoter status. The combined IDH/TERT classification divided Cohort 1 into four molecular groups with distinct outcomes. The overall survival (OS) was the shortest in IDH wild-type/TERT mutated groups, which mostly consisted of GBMs (P < 0.0001). To investigate the association between TERT mutations and MGMT methylation on survival of patients with GBM, samples from a combined cohort of 453 IDH-wild-type GBM cases treated with radiation and temozolomide were analyzed. A multivariate Cox regression model revealed that the interaction between TERT and MGMT was significant for OS (P = 0.0064). Compared with TERT mutant-MGMT unmethylated GBMs, the hazard ratio (HR) for OS incorporating the interaction was the lowest in the TERT mutant-MGMT methylated GBM (HR, 0.266), followed by the TERT wild-type-MGMT methylated (HR, 0.317) and the TERT wild-type-MGMT unmethylated GBMs (HR, 0.542). Thus, patients with TERT mutant-MGMT unmethylated GBM have the poorest prognosis. Our findings suggest that a combination of IDH, TERT, and MGMT refines the classification of grade II-IV diffuse gliomas.  
  Address Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. kichimur@ncc.go.jp  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2051-5960 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27503138 Approved no  
  Call Number ref @ user @ Serial 96639  
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