Investigating chromosomal instability in long-term survivors with glioblastoma and grade 4 astrocytoma

Jochem K. H. Spoor, May den Braber, Clemens M. F. Dirven, Adam Pennycuick, Jirina Bartkova, Jiri Bartek, Vera van Dis, Thierry P. P. van den Bosch, Sieger Leenstra, Subramanian Venkatesan

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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.
Original languageEnglish
Article number1218297
Number of pages9
JournalFrontiers in Oncology
Volume13
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
Copyright © 2024 Spoor, den Braber, Dirven, Pennycuick, Bartkova, Bartek, van Dis, van den Bosch, Leenstra and Venkatesan.

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