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Comprehensive molecular characterization of long-term glioblastoma survivors.
- Source :
-
Cancer letters [Cancer Lett] 2024 Jul 01; Vol. 593, pp. 216938. Date of Electronic Publication: 2024 May 10. - Publication Year :
- 2024
-
Abstract
- Fewer than 5 % glioblastoma (GBM) patients survive over five years and are termed long-term survivors (LTS), yet their molecular background is unclear. The present cohort included 72 isocitrate dehydrogenase (IDH)-wildtype GBM patients, consisting of 35 LTS and 37 short-term survivors (STS), and we employed whole exome sequencing, RNA-seq and DNA methylation array to delineate this largest LTS cohort to date. Although LTS and STS demonstrated analogous clinical characters and classical GBM biomarkers, CASC5 (P = 0.002) and SPEN (P = 0.013) mutations were enriched in LTS, whereas gene-to-gene fusions were concentrated in STS (P = 0.007). Importantly, LTS exhibited higher tumor mutation burden (P < 0.001) and copy number (CN) increase (P = 0.013), but lower mutant-allele tumor heterogeneity score (P < 0.001) and CN decrease (P = 0.026). Additionally, LTS demonstrated hypermethylated genome (P < 0.001) relative to STS. Differentially expressed and methylated genes both enriched in olfactory transduction. Further, analysis of the tumor microenvironment revealed higher infiltration of M1 macrophages (P = 0.043), B cells (P = 0.016), class-switched memory B cells (P = 0.002), central memory CD4 <superscript>+</superscript> T cells (P = 0.031) and CD4 <superscript>+</superscript> Th1 cells (P = 0.005) in LTS. We also separately analyzed a subset of patients who were methylation class-defined GBM, contributing 70.8 % of the entire cohort, and obtained similar results relative to prior analyses. Finally, we demonstrated that LTS and STS could be distinguished using a subset of molecular features. Taken together, the present study delineated unique molecular attributes of LTS GBM.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Female
Male
Middle Aged
Aged
Tumor Microenvironment genetics
Biomarkers, Tumor genetics
Adult
Exome Sequencing
Isocitrate Dehydrogenase genetics
Gene Expression Regulation, Neoplastic
DNA Copy Number Variations
Glioblastoma genetics
Glioblastoma pathology
Brain Neoplasms genetics
Brain Neoplasms pathology
DNA Methylation
Cancer Survivors
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 593
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 38734160
- Full Text :
- https://doi.org/10.1016/j.canlet.2024.216938