Genetic Alterations in Glioblastoma and Their Clinical Implications – A Comprehensive Review

Author(s) :

Alexandra Hanu1, Gențiana Ioana Eremia2, Marianne Elena Dina2, Andrei Șerban2, Georgiana Tănase2, Alexandra Neagu2


1 National Institute of Infectious Disease ” Prof. Dr Matei Bals” Bucharest, Romania

2 “Sf Ioan” Clinical Emergency Hospital Bucharest, Romania

Corresponding author: Alexandra Hanu, Email:

Published: III, 2, 1 October 2023, 38 - 46 DOI: 10.53011/JMRO.2023.02.05

Open Access

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October 1, 2023 0 Comments


Glioblastoma (GBM) is the most aggressive primary brain tumor with limited treatment options and poor prognosis. In recent years, molecular research has provided valuable insights into the underlying mechanisms of GBM, uncovering key molecular alterations and signaling pathways that drive tumor development and progression. Driver mutations play a critical role in the pathogenesis of glioblastoma (GBM), influencing tumor initiation, growth, and therapeutic response. Among the key driver mutations identified in GBM, the prominent example is the mutation of the epidermal growth factor receptor (EGFR) gene. Dysregulated signaling pathways, including the PI3K/Akt/mTOR, the Ras/Raf/MEK/ERK, and the NOTCH pathway play a critical role in cell proliferation, survival, and invasion in GBM. Epigenetic modifications contribute to tumor initiation, repression of the tumor suppressor genes, and therapy resistance. Global DNA hypomethylation, site-specific hypermethylation, histone deacetylase, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) are the most common epigenetic modifications. Immune checkpoints, such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are upregulated, leading to T-cell exhaustion and impaired antitumor immune responses. The molecular classification systems have provided a more refined understanding of GBM biology, have important implications for personalized treatment strategies, play a role in guiding clinical trials designed to specifically target and evaluate novel therapies in patients with specific molecular subtypes, and hold promise for predicting treatment response. The identification of molecular subtypes can be associated with different

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