1. TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations
- Author
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Yonehiro Kanemura, Masayuki Kanamori, Fumi Higuchi, Yoshitaka Narita, Ken ichiro Matsuda, Yukitomo Ishi, Shunsaku Takayanagi, Kuniaki Saito, Takashi Komori, Ryunosuke Machida, Yohei Miyake, Takashi Sasayama, Ryo Nishikawa, Yasuhiko Hattori, Ryusuke Hatae, Koichi Ichimura, Teiji Tominaga, Masahiro Mizoguchi, Ryohei Otani, Hiroyoshi Suzuki, Yoshiko Okita, Yuko Matsushita, Mitsutoshi Nakada, Shota Tanaka, Yukihiko Sonoda, Hikaru Sasaki, Masahiro Nonaka, Nobuhiro Hata, Motoo Nagane, Tomoko Shofuda, Haruhiko Kishima, Eriel Sandika Pareira, Takehiro Uda, Yasuji Miyakita, Taishi Nakamura, Aya Kuchiba, Shigeru Yamaguchi, Kazuhiko Kurozumi, Ryuta Saito, Keiichi Kobayashi, Junya Fukai, Hideyuki Arita, Kaoru Tamura, Tsukasa Sakaida, Makoto Shibuya, Toshihiko Iuchi, Makoto Ohno, Daisuke Sakamoto, Kai Yamasaki, Sho Tamai, and Kazuhiro Tanaka
- Subjects
Oncology ,Male ,medicine.medical_treatment ,1p/19q Codeletion ,Neurosurgical Procedures ,CDKN2A ,Promoter Regions, Genetic ,Telomerase ,Aged, 80 and over ,Brain Neoplasms ,Glioma ,Middle Aged ,Prognosis ,Isocitrate Dehydrogenase ,Survival Rate ,Chromosomes, Human, Pair 1 ,Cohort ,IDH1/2 ,Female ,Chromosome Deletion ,Adult ,medicine.medical_specialty ,IDH1 ,Adolescent ,TERT ,Oligodendroglioma ,Astrocytoma ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,Young Adult ,Internal medicine ,medicine ,Humans ,Karnofsky Performance Status ,Adverse effect ,Aged ,Proportional Hazards Models ,Retrospective Studies ,1p/19q codeletion ,business.industry ,Proportional hazards model ,Research ,medicine.disease ,Radiation therapy ,Multivariate Analysis ,Mutation ,Radiotherapy, Adjuvant ,Neurology (clinical) ,Neoplasm Grading ,business ,Glioblastoma ,Chromosomes, Human, Pair 19 - Abstract
TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90–100%) were associated with favorable prognosis (p TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.
- Published
- 2020