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, T. G., Alden, J., Dubuc, A. M., Welsh, C. T., Znoyko, I., Cooley, L. D., Farooqi, M. S., Schwartz, S., Li, Y. Y., Cherniack, A. D., Lindhorst, S. M., Gener, M., Wolff, D. J., Meredith, D. M. Near haploidization is a genomic hallmark which defines a molecular subgroup of giant cell glioblastoma. Neurooncol Adv 2, 155-155 (2020).
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