Prognostic Impact of TERT Promoter Mutations in Adult-Type Diffuse Gliomas Based on WHO2021 Criteria

被引：6

作者：

Lee, Yujin ^{[1
]}

Park, Chul-Kee ^{[2
]}

Park, Sung-Hye ^{[3
,4
]}

机构：

[1] Catholic Univ Korea, St Vincents Hosp, Dept Hosp Pathol, Coll Med, 93 Jungbu Daero, Suwon 16247, Gyeonggi Do, South Korea

[2] Seoul Natl Univ, Coll Med, Dept Neurosurg, 103 Deahak Ro, Seoul 03080, South Korea

[3] Seoul Natl Univ, Coll Med, Dept Pathol, 103 Deahak Ro, Seoul 03080, South Korea

[4] Seoul Natl Univ, Coll Med, Neurosci Inst, 103 Deahak Ro, Seoul 03080, South Korea

来源：

CANCERS | 2024年 / 16卷 / 11期

关键词：

genetics; glioblastoma; IDH-mutant astrocytoma; oligodendroglioma; MGMT promoter; TERT promoter; CENTRAL-NERVOUS-SYSTEM; GRADE; IDH; TUMORS; CLASSIFICATION; RECURRENT; IMETELSTAT; DIAGNOSIS; CHILDREN; SURVIVAL;

D O I：

10.3390/cancers16112032

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Mutation in the telomerase reverse transcriptase promoter (TERTp )is commonly observed in various malignancies, such as central nervous system (CNS) tumors, malignant melanoma, bladder cancer, and thyroid carcinoma. These mutations are recognized as significant poor prognostic factors for these tumors. In this investigation, a total of 528 cases of adult-type diffuse gliomas diagnosed at a single institution were reclassified according to the 2021 WHO classifications of CNS tumors, 5th edition (WHO2021). The study analyzed clinicopathological and genetic features, including TERTp mutations in each tumor. The impact of known prognostic factors on patient outcomes was analyzed through Kaplan-Meier survival and Cox regression analysis. TERTp mutations were predominantly identified in 94.1% of oligodendrogliomas (ODG), followed by 66.3% in glioblastoma, IDH-wildtype (GBM-IDHwt), and 9.2% of astrocytomas, IDH-mutant (A-IDHm). When considering A-IDHm and GBM as astrocytic tumors (Group 1) and ODGs (Group 2), TERTp mutations emerged as a significant adverse prognostic factor (p = 0.013) in Group 1. However, within each GBM-IDHwt and A-IDHm, the presence of TERTp mutations did not significantly impact patient prognosis (p = 0.215 and 0.268, respectively). Due to the high frequency of TERTp mutations in Group 2 (ODG) and their consistent prolonged survival, a statistical analysis to evaluate their impact on overall survival was deemed impractical. When considering MGMTp status, the combined TERTp-mutated and MGMTp-unmethylated group exhibited the worst prognosis in OS (p = 0.018) and PFS (p = 0.034) of GBM. This study confirmed that the classification of tumors according to the WHO2021 criteria effectively reflected prognosis. Both uni- and multivariate analyses in GBM, age, MGMTp methylation, and CDKN2A/B homozygous deletion were statistically significant prognostic factors while in univariate analysis in A-IDHm, grade 4, the Ki-67 index and MYCN amplifications were statistically significant prognostic factors. This study suggests that it is important to classify and manage tumors based on their genetic characteristics in adult-type diffuse gliomas.

引用

页数：19

共 66 条

[1] Prognostic relevance of genetic alterations in diffuse lower-grade gliomas [J].

Aoki, Kosuke ;

Nakamura, Hideo ;

Suzuki, Hiromichi ;

Matsuo, Keitaro ;

Kataoka, Keisuke ;

Shimamura, Teppei ;

Motomura, Kazuya ;

Ohka, Fumiharu ;

Shiina, Satoshi ;

Yamamoto, Takashi ;

Nagata, Yasunobu ;

Yoshizato, Tetsuichi ;

Mizoguchi, Masahiro ;

Abe, Tatsuya ;

Momii, Yasutomo ;

Muragaki, Yoshihiro ;

Watanabe, Reiko ;

Ito, Ichiro ;

Sanada, Masashi ;

Yajima, Hironori ;

Morita, Naoya ;

Takeuchi, Ichiro ;

Miyano, Satoru ;

Wakabayashi, Toshihiko ;

Ogawa, Seishi ;

Natsume, Atsushi .

NEURO-ONCOLOGY, 2018, 20 (01) :66-77

[2] CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDH-mutant gliomas [J].

Appay, Romain ;

Dehais, Caroline ;

Maurage, Claude-Alain ;

Alentorn, Agusti ;

Carpentier, Catherine ;

Colin, Carole ;

Ducray, Francois ;

Escande, Fabienne ;

Idbaih, Ahmed ;

Kamoun, Aurelie ;

Marie, Yannick ;

Mokhtari, Karima ;

Tabouret, Emeline ;

Trabelsi, Nesrine ;

Uro-Coste, Emmanuelle ;

Delattre, Jean-Yves ;

Figarella-Branger, Dominique ;

Desenclos, C. ;

Sevestre, H. ;

Menei, P. ;

Rousseau, A. ;

Cruel, T. ;

Lopez, S. ;

Mihai, M-I. ;

Petit, A. ;

Adam, C. ;

Parker, F. ;

Dam-Hieu, P. ;

Quintin-Roue, I. ;

Eimer, S. ;

Loiseau, H. ;

Bekaert, L. ;

Chapon, F. ;

Ricard, D. ;

Godfraind, C. ;

Khallil, T. ;

Cazals-Hatem, D. ;

Faillot, T. ;

Gaultier, C. ;

Tortel, M. C. ;

Carpiuc, I. ;

Richard, P. ;

Lahiani, W. ;

Aubriot-Lorton, H. ;

Ghiringhelli, F. ;

Maurage, C. A. ;

Ramirez, C. ;

Gueye, E. M. ;

Labrousse, F. ;

Chinot, O. .

NEURO-ONCOLOGY, 2019, 21 (12) :1519-1528

[3] Telomerase inhibition is an effective therapeutic strategy in TERT promoter-mutant glioblastoma models with low tumor volume [J].

Aquilanti, Elisa ;

Kageler, Lauren ;

Watson, Jacqueline ;

Baird, Duncan M. ;

Jones, Rhiannon E. ;

Hodges, Marie ;

Szegletes, Zsofia M. ;

Doench, John G. ;

Strathdee, Craig A. ;

Figueroa, Jose Ricardo Mc Faline ;

Ligon, Keith L. ;

Beck, Matthew ;

Wen, Patrick Y. ;

Meyerson, Matthew .

NEURO-ONCOLOGY, 2023, 25 (07) :1275-1285

[4] Telomerase as a therapeutic target in glioblastoma [J].

Aquilanti, Elise ;

Kageler, Lauren ;

Wen, Patrick Y. ;

Meyerson, Matthew .

NEURO-ONCOLOGY, 2021, 23 (12) :2004-2013

[5] Prognostic significance of TERT promoter mutations in adult-type diffuse gliomas [J].

Arita, Hideyuki ;

Ichimura, Koichi .

BRAIN TUMOR PATHOLOGY, 2022, 39 (03) :121-129

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

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 Sandika ;

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 .

ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2020, 8 (01)

[7] A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas [J].

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 .

ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2016, 4 :79

[8] Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss [J].

Arita, Hideyuki ;

Narita, Yoshitaka ;

Fukushima, Shintaro ;

Tateishi, Kensuke ;

Matsushita, Yuko ;

Yoshida, Akihiko ;

Miyakita, Yasuji ;

Ohno, Makoto ;

Collins, V. Peter ;

Kawahara, Nobutaka ;

Shibui, Soichiro ;

Ichimura, Koichi .

ACTA NEUROPATHOLOGICA, 2013, 126 (02) :267-276

[9] The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism [J].

Batista, Rui ;

Cruvinel-Carloni, Adriana ;

Vinagre, Joao ;

Peixoto, Joana ;

Catarino, Telmo A. ;

Campanella, Nathalia Cristina ;

Menezes, Weder ;

Becker, Aline Paixao ;

de Almeida, Gisele Caravina ;

Matsushita, Marcus M. ;

Clara, Carlos ;

Neder, Luciano ;

Viana-Pereira, Marta ;

Honavar, Mrinalini ;

Castro, L. Igia ;

Lopes, Jose Manuel ;

Carvalho, Bruno ;

Vaz, Rui Manuel ;

Maximo, Valdemar ;

Soares, Paula ;

Sobrinho-Simoes, Manuel ;

Reis, Rui Manuel ;

Lima, Jorge .

INTERNATIONAL JOURNAL OF CANCER, 2016, 139 (02) :414-423

[10] IDH-wildtype lower-grade diffuse gliomas: the importance of histological grade and molecular assessment for prognostic stratification [J].

Berzero, Giulia ;

Di Stefano, Anna Luisa ;

Ronchi, Susanna ;

Bielle, Franck ;

Villa, Chiara ;

Guillerm, Erell ;

Capelle, Laurent ;

Mathon, Bertrand ;

Laurenge, Alice ;

Giry, Marine ;

Schmitt, Yohann ;

Marie, Yannick ;

Idbaih, Ahmed ;

Hoang-Xuan, Khe ;

Delattre, Jean-Yves ;

Mokhtari, Karima ;

Sanson, Marc .

NEURO-ONCOLOGY, 2021, 23 (06) :955-966

← 1 2 3 4 5 6 7 →