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Whole-exome sequencing revealed mutational profiles of giant cell glioblastomas.

Authors
  • Shi, Zhi-Feng1
  • Li, Kay Ka-Wai2, 3
  • Kwan, Johnny Sheung Him2
  • Yang, Rui Ryan2
  • Aibaidula, Abudumijiti1
  • Tang, Qisheng1
  • Bao, Yifeng1
  • Mao, Ying1
  • Chen, Hong4
  • Ng, Ho-Keung2, 3
  • 1 Department of Neurosurgery, Huashan Hospital, Fudan University, Wulumuqi Zhong Road 12, Shanghai, 200040, China. , (China)
  • 2 Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong, China. , (China)
  • 3 Shenzhen Research Institute, The Chinese University of Hong Kong, No.10, 2nd Yuexing Road, Nanshan District, Shenzhen, 518057, China. , (China)
  • 4 Department of Pathology, Huashan Hospital, Fudan University, Wulumuqi Zhong Road 12, Shanghai, 200040, China. , (China)
Type
Published Article
Journal
Brain Pathology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Nov 01, 2019
Volume
29
Issue
6
Pages
782–792
Identifiers
DOI: 10.1111/bpa.12720
PMID: 30861589
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Giant cell glioblastoma (gcGBM) is a rare histological variant of GBM, accounting for about 1% of all GBM. The prognosis is poor generally though gcGBM does slightly better than the other IDH-wild-type GBM. Because of the rarity of the cases, there has been no comprehensive molecular analysis of gcGBM. Previously, single-gene study identified genetic changes in TP53, PTEN and TERT promoter mutation in gcGBM. In this report, we performed whole-exome sequencing (WES) to identify somatically acquired mutations and copy number variations (CNVs) in 10 gcGBM genomes. We also examined TERT promoter mutation and MGMT methylation in our cohort. On top of the reported mutations, WES revealed ATRX, PIK3R1, RB1 and SETD2 as the recurrent mutations in gcGBM. Notably, one tumor harbored a mutation in MutS homolog 6 (MSH6) that is a key mismatch repair (MMR) gene. This tumor demonstrated hypermutation phenotype and showed an increased number of somatic mutations. TERT promoter mutation and MGMT methylation were observed in 20% and 40% of our samples, respectively. In conclusion, we described relevant mutation profiling for developing future targeted therapies in gcGBM. © 2019 International Society of Neuropathology.

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