TERT promoter mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic glioma with molecular features of glioblastoma.

Adult Brain Neoplasms / diagnosis DNA Copy Number Variations / genetics Female Glioma / diagnosis Homozygote Humans Isocitrate Dehydrogenase / genetics Male Middle Aged Mutation / genetics PTEN Phosphohydrolase / genetics Sequence Deletion / genetics Telomerase / genetics
Copy-number alteration IDH-wildtype Lower grade glioma TERT promoter mutation

Journal

Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041

Informations de publication

Date de publication:
08 2021
Historique:
received: 02 06 2021
accepted: 10 06 2021
revised: 10 06 2021
pubmed: 21 6 2021
medline: 14 1 2022
entrez: 20 6 2021
Statut: ppublish

Résumé

The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) update 3 recommends that histologic grade II and III IDH-wildtype diffuse astrocytic gliomas that harbor EGFR amplification, the combination of whole chromosome 7 gain and whole chromosome 10 loss (7 + /10 -), or TERT promoter (pTERT) mutations should be considered as glioblastomas (GBM), World Health Organization grade IV. In this retrospective study, we examined the utility of molecular classification based on pTERT status and copy-number alterations (CNAs) in IDH-wildtype lower grade gliomas (LGGs, grade II, and III). The impact on survival was evaluated for the pTERT mutation and CNAs, including EGFR gain/amplification, PTEN loss, CDKN2A homozygous deletion, and PDGFRA gain/amplification. We analyzed 46 patients with IDH-wildtype/pTERT-mutant (mut) LGGs and 85 with IDH-wildtype/pTERT-wildtype LGGs. EGFR amplification and a combination of EGFR gain and PTEN loss (EGFR + /PTEN -) were significantly more frequent in pTERT-mut patients (p < 0.0001). Cox regression analysis showed that the pTERT mutation was a significant predictor of poor prognosis (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.55-4.89, p = 0.0008), but neither EGFR amplification nor EGFR + /PTEN - was an independent prognostic factor in IDH-wildtype LGGs. PDGFRA gain/amplification was a significant poor prognostic factor in IDH-wildtype/pTERT-wildtype LGGs (HR 2.44, 95% CI 1.09-5.27, p = 0.03, Cox regression analysis). The IDH-wildtype LGGs with either pTERT-mut or PDGFRA amplification were mostly clustered with GBM by DNA methylation analysis. Thus, our study suggests that analysis of pTERT mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic gliomas with molecular features of glioblastoma. The PDGFRA status may help further delineate IDH-wildtype/pTERT-wildtype LGGs. Methylation profiling showed that IDH-wildtype LGGs without molecular features of GBM were a heterogeneous group of tumors. Some of them did not fall into existing categories and had significantly better prognoses than those clustered with GBM.

Identifiants

DOI: 10.1007/s00401-021-02337-9 PMID: 34148105
pubmed: 34148105
doi: 10.1007/s00401-021-02337-9
pii: 10.1007/s00401-021-02337-9
doi:

Substances chimiques

Isocitrate Dehydrogenase EC 1.1.1.41
TERT protein, human EC 2.7.7.49
Telomerase EC 2.7.7.49
PTEN Phosphohydrolase EC 3.1.3.67
PTEN protein, human EC 3.1.3.67

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

323-338

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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Auteurs

Kenji Fujimoto (K)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Neurosurgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.

Hideyuki Arita (H)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.

Kaishi Satomi (K)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.

Kai Yamasaki (K)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Pediatric Hematology and Oncology, Osaka City General Hospital, Osaka, Japan.

Yuko Matsushita (Y)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.

Taishi Nakamura (T)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

Yasuji Miyakita (Y)

Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.

Toru Umehara (T)

Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.

Keiichi Kobayashi (K)

Department of Neurosurgery, Faculty of Medicine, Kyorin University, Tokyo, Japan.

Kaoru Tamura (K)

Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan.

Shota Tanaka (S)

Department of Neurosurgery, The University of Tokyo, Tokyo, Japan.

Fumi Higuchi (F)

Department of Neurosurgery, Dokkyo Medical University, Tochigi, Japan.

Yoshiko Okita (Y)

Department of Neurosurgery, Osaka International Cancer Institute, Osaka, Japan.

Yonehiro Kanemura (Y)

Department of Biomedical Research and Innovation, Institute for Clinical Research, National Hospital Organization Osaka National Hospital, Osaka, Japan.

Junya Fukai (J)

Department of Neurological Surgery, Wakayama Medical University, Wakayama, Japan.

Daisuke Sakamoto (D)

Department of Neurosurgery, Hyogo College of Medicine, Hyogo, Japan.

Takehiro Uda (T)

Department of Neurosurgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Ryunosuke Machida (R)

Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Tokyo, Japan.

Aya Kuchiba (A)

Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan.

Taketoshi Maehara (T)

Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan.

Motoo Nagane (M)

Department of Neurosurgery, Faculty of Medicine, Kyorin University, Tokyo, Japan.

Ryo Nishikawa (R)

Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan.

Hiroyoshi Suzuki (H)

Department of Pathology and Laboratory Medicine, National Hospital Organization, Sendai Medical Center, Sendai, Japan.

Makoto Shibuya (M)

Central Clinical Laboratory, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.

Takashi Komori (T)

Department of Laboratory Medicine and Pathology (Neuropathology), Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.

Yoshitaka Narita (Y)

Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.

Koichi Ichimura (K)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. k.ichimura.uk@juntendo.ac.jp.
Department of Brain Disease Translational Research, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. k.ichimura.uk@juntendo.ac.jp.
ORCID: 0000-0002-3851-2349

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Homozygote › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › NAD (+) and NADP (+) dependent Alcohol oxidoreductases › Isocitrate dehydrogenases › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Phosphohydrolase PTEN › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Phénomènes génétiques › Mutagenèse › Délétion de séquence › TERT promoter mutation status is necessary and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Ribonucléoprotéines › Telomerase › TERT promoter mutation status is necessary and...