ノナカ　マサヒロ   NONAKA MASAHIRO   埜中　正博    所属   関西医科大学  脳神経外科学講座    職種   教授
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas.
掲載誌名	正式名：Acta neuropathologica communications 略　 称：Acta Neuropathol Commun ISSNコード：2051596020515960
巻・号・頁	4(1),pp.79
著者・共著者	Arita Hideyuki, Yamasaki Kai, Matsushita Yuko, Nakamura Taishi, Shimokawa Asanao, Takami Hirokazu, Tanaka Shota, Mukasa Akitake, Shirahata Mitsuaki, Shimizu Saki, Suzuki Kaori, Saito Kuniaki, Kobayashi Keiichi, Higuchi Fumi, Uzuka Takeo, Otani Ryohei, Tamura Kaoru, Sumita Kazutaka, Ohno Makoto, Miyakita Yasuji, Kagawa Naoki, Hashimoto Naoya, Hatae Ryusuke, Yoshimoto Koji, Shinojima Naoki, Nakamura Hideo, Kanemura Yonehiro, Okita Yoshiko, Kinoshita Manabu, Ishibashi Kenichi, Shofuda Tomoko, Kodama Yoshinori, Mori Kanji, Tomogane Yusuke, Fukai Junya, Fujita Koji, Terakawa Yuzo, Tsuyuguchi Naohiro, Moriuchi Shusuke, Nonaka Masahiro, Suzuki Hiroyoshi, Shibuya Makoto, Maehara Taketoshi, Saito Nobuhito, Nagane Motoo, Kawahara Nobutaka, Ueki Keisuke, Yoshimine Toshiki, Miyaoka Etsuo, Nishikawa Ryo, Komori Takashi, Narita Yoshitaka, Ichimura Koichi
発行年月	2016/08
概要	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.
DOI	10.1186/s40478-016-0351-2
PMID	27503138