- Main
TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations.
- Arita, Hideyuki;
- Matsushita, Yuko;
- Machida, Ryunosuke;
- Yamasaki, Kai;
- Hata, Nobuhiro;
- Ohno, Makoto;
- Yamaguchi, Shigeru;
- Sasayama, Takashi;
- Tanaka, Shota;
- Higuchi, Fumi;
- Iuchi, Toshihiko;
- Saito, Kuniaki;
- Kanamori, Masayuki;
- Matsuda, Ken-Ichiro;
- Miyake, Yohei;
- Tamura, Kaoru;
- Tamai, Sho;
- Nakamura, Taishi;
- Uda, Takehiro;
- Okita, Yoshiko;
- Fukai, Junya;
- Sakamoto, Daisuke;
- Hattori, Yasuhiko;
- Pareira, Eriel;
- Hatae, Ryusuke;
- Ishi, Yukitomo;
- Miyakita, Yasuji;
- Tanaka, Kazuhiro;
- Takayanagi, Shunsaku;
- Otani, Ryohei;
- Sakaida, Tsukasa;
- Kobayashi, Keiichi;
- Saito, Ryuta;
- Kurozumi, Kazuhiko;
- Shofuda, Tomoko;
- Nonaka, Masahiro;
- Suzuki, Hiroyoshi;
- Shibuya, Makoto;
- Komori, Takashi;
- Sasaki, Hikaru;
- Mizoguchi, Masahiro;
- Kishima, Haruhiko;
- Nakada, Mitsutoshi;
- Sonoda, Yukihiko;
- Tominaga, Teiji;
- Nagane, Motoo;
- Nishikawa, Ryo;
- Kanemura, Yonehiro;
- Kuchiba, Aya;
- Narita, Yoshitaka;
- Ichimura, Koichi
- et al.
Published Web Location
https://doi.org/10.1186/s40478-020-01078-2Abstract
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 < 0.05). A multivariable Cox regression model revealed that 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.
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