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  • Title: TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations.
    Author: Arita H, Matsushita Y, Machida R, Yamasaki K, Hata N, Ohno M, Yamaguchi S, Sasayama T, Tanaka S, Higuchi F, Iuchi T, Saito K, Kanamori M, Matsuda KI, Miyake Y, Tamura K, Tamai S, Nakamura T, Uda T, Okita Y, Fukai J, Sakamoto D, Hattori Y, Pareira ES, Hatae R, Ishi Y, Miyakita Y, Tanaka K, Takayanagi S, Otani R, Sakaida T, Kobayashi K, Saito R, Kurozumi K, Shofuda T, Nonaka M, Suzuki H, Shibuya M, Komori T, Sasaki H, Mizoguchi M, Kishima H, Nakada M, Sonoda Y, Tominaga T, Nagane M, Nishikawa R, Kanemura Y, Kuchiba A, Narita Y, Ichimura K.
    Journal: Acta Neuropathol Commun; 2020 Nov 23; 8(1):201. PubMed ID: 33228806.
    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.
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