Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma

Acta Neuropathologica
Qun LiuWei Zhang

Abstract

Ten to twenty percent of newly diagnosed glioblastoma (GBM) patients initially present with multiple lesions, termed multifocal or multicentric GBM (M-GBM). The prognosis of these patients is poorer than that of solitary GBM (S-GBM) patients. However, it is unknown whether multifocality has a genetic, epigenetic, or molecular basis. Here, we identified the genetic and epigenetic characteristics of M-GBM by performing a comprehensive analysis of multidimensional data, including imaging, genetic, epigenetic, and gene expression profiles, from 30 M-GBM cases in The Cancer Genome Atlas database and comparing the results with those of 173 S-GBM cases. We found that M-GBMs had no IDH1, ATRX, or PDGFRA mutations and were significantly associated with the mesenchymal subtype. We also identified the CYB5R2 gene to be hypo-methylated and overexpressed in M-GBMs. The expression level of CYB5R2 was significantly associated with patient survival in two major independent GBM cohorts, totaling 758 cases. The IDH1 mutation was markedly associated with CYB5R2 promoter methylation, but the survival influence of CYB5R2 was independent of IDH1 mutation status. CYB5R2 expression was significantly associated with collagen maturation and the cataboli...Continue Reading

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Citations

Feb 18, 2016·Chinese Medical Journal·Qiu-Ju LiCheng-Yin Liu
May 6, 2016·Frontiers in Surgery·Amy BradshawTinte Itinteang
Jun 12, 2016·Briefings in Functional Genomics·Veronique G LeBlanc, Marco A Marra
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Sep 12, 2019·Frontiers in Oncology·Jo-Heon KimKyung-Hwa Lee
Sep 9, 2017·Advances in Anatomic Pathology·Murat Gokden
Feb 19, 2020·FEBS Open Bio·Fuhua YangQilin Huang
May 23, 2020·Journal of Neuro-oncology·Antonio DonoYoshua Esquenazi
Aug 23, 2017·Computational and Mathematical Methods in Medicine·Tabea TreppmannManuela Zucknick
Dec 29, 2020·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Yao LiSheng-Qing Lv
Jan 16, 2021·Chinese Neurosurgical Journal·Zuo-Xin ZhangSheng-Qing Lv
Feb 15, 2021·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Alexandra Benouaich-AmielShlomit Yust-Katz
Jan 9, 2021·Signal Transduction and Targeted Therapy·Sijia LiuPeter Ten Dijke
Aug 30, 2021·Radiation Oncology·Daniel Felix FleischmannMaximilian Niyazi

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