Spoor, JKH;
den Braber, M;
Dirven, CMF;
Pennycuick, A;
Bartkova, J;
Bartek, J;
van Dis, V;
... Venkatesan, S; + view all
(2023)
Investigating chromosomal instability in long-term survivors with glioblastoma and grade 4 astrocytoma.
Frontiers in Oncology
, 13
, Article 1218297. 10.3389/fonc.2023.1218297.
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Abstract
BACKGROUND: Only a small group of patients with glioblastoma multiforme (GBM) survives more than 36 months, so-called long-term survivors. Recent studies have shown that chromosomal instability (CIN) plays a prognostic and predictive role among different cancer types. Here, we compared histological (chromosome missegregation) and bioinformatic metrics (CIN signatures) of CIN in tumors of GBM typical survivors (≤36 months overall survival), GBM long-term survivors and isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytomas. METHODS: Tumor sections of all gliomas were examined for anaphases and chromosome missegregation. Further CIN signature activity analysis in the The Cancer Genome Atlas (TCGA)-GBM cohort was performed. RESULTS: Our data show that chromosome missegregation is pervasive in high grade gliomas and is not different between the 3 groups. We find only limited evidence of altered CIN levels in tumors of GBM long-term survivors relative to the other groups, since a significant depletion in CIN signature 11 relative to GBM typical survivors was the only alteration detected. In contrast, within IDH-mutant grade 4 astrocytomas we detected a significant enrichment of CIN signature 5 and 10 activities and a depletion of CIN signature 1 activity relative to tumors of GBM typical survivors. CONCLUSIONS: Our data suggest that CIN is pervasive in high grade gliomas, however this is unlikely to be a major contributor to the phenomenon of long-term survivorship in GBM. Nevertheless, further evaluation of specific types of CIN (signatures) could have prognostic value in patients suffering from grade 4 gliomas.
| Type: | Article |
|---|---|
| Title: | Investigating chromosomal instability in long-term survivors with glioblastoma and grade 4 astrocytoma |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fonc.2023.1218297 |
| Publisher version: | http://dx.doi.org/10.3389/fonc.2023.1218297 |
| Language: | English |
| Additional information: | © 2024 Spoor, den Braber, Dirven, Pennycuick, Bartkova, Bartek, van Dis, van den Bosch, Leenstra and Venkatesan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | high grade glioma, glioblastoma multiforme, astrocytoma, chromosomal instability, genome instability, IDH |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10186291 |
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