Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1.
Acta Neuropathol
; 142(1): 179-189, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-33876327
ABSTRACT
Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Proteína Supressora de Tumor p53
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Tumores Neuroectodérmicos Primitivos
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Glioblastoma
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Metilação de DNA
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Ubiquitina-Proteína Ligases
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PTEN Fosfo-Hidrolase
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Proteínas de Ligação a Retinoblastoma
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Acta Neuropathol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha