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Molecular landscape of IDH-wild-type, H3-wild-type glioblastomas of adolescents and young adults.
Shi, Zhi-Feng; Li, Kay Ka-Wai; Huang, Queenie Jun-Qi; Wang, Wei-Wei; Kwan, Johnny Sheung-Him; Chen, Hong; Liu, Xiang-Zhi; Li, Wen-Cai; Chan, Danny Tat-Ming; Zhang, Zhen-Yu; Mao, Ying; Ng, Ho-Keung.
Afiliação
  • Shi ZF; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
  • Li KK; Hong Kong and Shanghai Brain Consortium (HSBC), Hong Kong, China.
  • Huang QJ; Hong Kong and Shanghai Brain Consortium (HSBC), Hong Kong, China.
  • Wang WW; Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.
  • Kwan JS; Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.
  • Chen H; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • Liu XZ; Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.
  • Li WC; Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China.
  • Chan DT; Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • Zhang ZY; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • Mao Y; Division of Neurosurgery, Department of Surgery, Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Ng HK; Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Neuropathol Appl Neurobiol ; 48(4): e12802, 2022 06.
Article em En | MEDLINE | ID: mdl-35191072
OBJECTIVE: We aimed to characterise glioblastomas of adolescents and young adults (AYAs) that were isocitrate dehydrogenase (IDH) wild type (wt) and H3wt. MATERIALS AND METHODS: Fifty such patients (aged 16-32) were studied by methylation profiling, targeted sequencing and targeted RNA-seq. RESULTS: Tumours predominantly clustered into three methylation classes according to the terminology of Capper et al. (2018): (anaplastic) pleomorphic xanthoastrocytoma (PXA) (21 cases), GBM_midline (15 cases) and glioblastoma RTK/mesenchymal (seven cases). Two cases clustered with ANA_PA, four cases with LGG classes and one with GBM_MYCN. Only fifteen cases reached a calibrated score >0.84 when the cases were uploaded to DKFZ Classifier. GBM_midline-clustered tumours had a poorer overall survival (OS) compared with the PXA-clustered tumours (p = 0.030). LGG-clustered cases had a significantly better survival than GBM_midline-clustered tumours and glioblastoma RTK/mesenchymal-clustered tumours. Only 13/21 (62%) of PXA-clustered cases were BRAF V600E mutated. Most GBM_midline-clustered cases were not located in the midline. GBM_midline-clustered cases were characterised by PDGFRA amplification/mutation (73.3%), mutations of mismatch repair genes (40.0%), and all showed H3K27me3 and EZH1P loss, and an unmethylated MGMT promoter. Across the whole cohort, MGMT promoter methylation and wt TERT promoter were favourable prognosticators. Mismatch repair gene mutations were poor prognosticators and together with methylation class and MGMT methylation, maintained their significance in multivariate analyses. BRAF mutation was a good prognosticator in the PXA-clustered tumours. CONCLUSION: Methylation profiling is a useful tool in the diagnosis and prognostication of AYA glioblastomas, and the methylation classes have distinct molecular characteristics. The usual molecular diagnostic criteria for adult IDHwt glioblastoma should be applied with caution within the AYA age group.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Astrocitoma / Neoplasias Encefálicas / Glioblastoma Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Humans Idioma: En Revista: Neuropathol Appl Neurobiol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Astrocitoma / Neoplasias Encefálicas / Glioblastoma Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Humans Idioma: En Revista: Neuropathol Appl Neurobiol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China