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. 2020 Nov 23;8(1):201.
doi: 10.1186/s40478-020-01078-2.

TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations

Hideyuki Arita  1   2 , Yuko Matsushita  3   4 , Ryunosuke Machida  5 , Kai Yamasaki  3   6 , Nobuhiro Hata  7 , Makoto Ohno  4 , Shigeru Yamaguchi  8 , Takashi Sasayama  9 , Shota Tanaka  10 , Fumi Higuchi  11 , Toshihiko Iuchi  12 , Kuniaki Saito  13 , Masayuki Kanamori  14 , Ken-Ichiro Matsuda  15 , Yohei Miyake  16   17 , Kaoru Tamura  18 , Sho Tamai  19 , Taishi Nakamura  17 , Takehiro Uda  20 , Yoshiko Okita  21   22 , Junya Fukai  23 , Daisuke Sakamoto  24 , Yasuhiko Hattori  25 , Eriel Sandika Pareira  26 , Ryusuke Hatae  7 , Yukitomo Ishi  8 , Yasuji Miyakita  4 , Kazuhiro Tanaka  9 , Shunsaku Takayanagi  10 , Ryohei Otani  11   27 , Tsukasa Sakaida  12 , Keiichi Kobayashi  13 , Ryuta Saito  14 , Kazuhiko Kurozumi  25 , Tomoko Shofuda  28 , Masahiro Nonaka  21   29 , Hiroyoshi Suzuki  30 , Makoto Shibuya  31 , Takashi Komori  32 , Hikaru Sasaki  26 , Masahiro Mizoguchi  7 , Haruhiko Kishima  33 , Mitsutoshi Nakada  19 , Yukihiko Sonoda  15 , Teiji Tominaga  14 , Motoo Nagane  13 , Ryo Nishikawa  16 , Yonehiro Kanemura  21   28 , Aya Kuchiba  5 , Yoshitaka Narita  4 , Koichi Ichimura  34
Affiliations

TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations

Hideyuki Arita et al. Acta Neuropathol Commun. .

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 < 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.

Keywords: 1p/19q codeletion; CDKN2A; Glioma; IDH1/2; TERT.

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Conflict of interest statement

The authors declare no conflicts of interest in association with this paper.

Figures

Fig. 1
Fig. 1
Kaplan-Meier analysis for OS in IDH-mutated gliomas when stratified by TERT and 1p/19q status (n = 560). TERT-mutated-1p/19q intact group showed an intermediate survival curve between TERT-mutated-1p/19q codeleted and TERT-wildtype-1p/19q intact groups, although the differences were not statistically significant. codel, codeleted; OS, overall survival; and 5yOS, 5-year overall survival
Fig. 2
Fig. 2
Survival impact of TERT and 1p/19q statuses in grade II–III gliomas when stratified by Karnofsky Performance Status (KPS) scores. a OS of WHO grade II–III cases (n = 527) stratified by the TERT and 1p/19q statuses. Survival curves of TERT-mutated-1p/19q intact group and TERT-mutated-1p/19q codeleted group were mostly overlapping. b OS of WHO grade IV cases (n = 33) stratified by the TERT and 1p/19q statuses. TERT-mutated-1p/19q intact group showed a tendency towards longer survival compared with that of the TERT-wildtype-1p/19q intact group although the difference was not significant. c TERT-mutated-1p/19q intact cases with a high KPS score (90 or 100) had a favorable prognosis comparable to that of the TERT-mutated-1p/19q codeleted cases. D. When analyzed in the population with a KPS score below 90, TERT mutation without 1p/19q codeletion did not show survival benefit. codel, codeleted; KPS, Karnofsky Performance Status; OS, overall survival.; 5yOS, 5-year overall survival
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References

    1. Aihara K, Mukasa A, Nagae G, Nomura M, Yamamoto S, Ueda H, Tatsuno K, Shibahara J, Takahashi M, Momose T, et al. Genetic and epigenetic stability of oligodendrogliomas at recurrence. Acta Neuropathol Commun. 2017;5:18. doi: 10.1186/s40478-017-0422-z. - DOI - PMC - PubMed
    1. Aoki K, Nakamura H, Suzuki H, Matsuo K, Kataoka K, Shimamura T, Motomura K, Ohka F, Shiina S, Yamamoto T, et al. Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. Neuro Oncol. 2018;20:66–77. doi: 10.1093/neuonc/nox132. - DOI - PMC - PubMed
    1. Appay R, Dehais C, Maurage CA, Alentorn A, Carpentier C, Colin C, Ducray F, Escande F, Idbaih A, Kamoun A, et al. CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDH-mutant gliomas. Neuro Oncol. 2019;21:1519–1528. doi: 10.1093/neuonc/noz124. - DOI - PMC - PubMed
    1. Arita H, Narita Y, Fukushima S, Tateishi K, Matsushita Y, Yoshida A, Miyakita Y, Ohno M, Collins VP, Kawahara N, et al. Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol. 2013;126:267–276. doi: 10.1007/s00401-013-1141-6. - DOI - PubMed
    1. Arita H, Narita Y, Matsushita Y, Fukushima S, Yoshida A, Takami H, Miyakita Y, Ohno M, Shibui S, Ichimura K. Development of a robust and sensitive pyrosequencing assay for the detection of IDH1/2 mutations in gliomas. Brain Tumor Pathol. 2015;32:22–30. doi: 10.1007/s10014-014-0186-0. - DOI - PubMed

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