Document Type
Article
Publication Date
11-12-2020
Identifier
DOI: 10.1093/noajnl/vdaa155; PMCID: PMC7764500
Abstract
Background: Giant cell glioblastoma (gcGBM) is a rare histologic subtype of glioblastoma characterized by numerous bizarre multinucleate giant cells and increased reticulin deposition. Compared with conventional isocitrate dehydrogenase (IDH)-wildtype glioblastomas, gcGBMs typically occur in younger patients and are generally associated with an improved prognosis. Although prior studies of gcGBMs have shown enrichment of genetic events, such as
Methods: Through a multi-institutional collaborative effort, we characterized 10 gcGBMs by chromosome studies, single nucleotide polymorphism microarray analysis, and targeted next-generation sequencing. These tumors were subsequently compared to the genomic and epigenomic profile of glioblastomas described in The Cancer Genome Atlas (TCGA) dataset.
Results: Our analysis identified a specific pattern of genome-wide massive loss of heterozygosity (LOH) driven by near haploidization in a subset of glioblastomas with giant cell histology. We compared the genomic signature of these tumors against that of all glioblastomas in the TCGA dataset (
Conclusions: Massive LOH driven by haploidization represents a defining molecular hallmark of a subtype of gcGBM. This unusual mechanism of tumorigenesis provides a diagnostic genomic hallmark to evaluate in future cases, may explain reported differences in survival, and suggests new therapeutic vulnerabilities.
Journal Title
Neurooncol Adv
Volume
2
Issue
1
First Page
155
Last Page
155
Keywords
giant cell glioblastoma; glioblastoma; loss of heterozygosity; near haploidization.
Recommended Citation
Baker TG, Alden J, Dubuc AM, et al. Near haploidization is a genomic hallmark which defines a molecular subgroup of giant cell glioblastoma. Neurooncol Adv. 2020;2(1):vdaa155. Published 2020 Nov 12. doi:10.1093/noajnl/vdaa155
Comments
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher's Link: https://academic.oup.com/noa/article/2/1/vdaa155/5979493