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Review
. 2024 Sep 4;29(1):451.
doi: 10.1186/s40001-024-02043-8.

Chromosomal instability: a key driver in glioma pathogenesis and progression

Adele Mazzoleni #  1 , Wireko Andrew Awuah #  2 , Vivek Sanker  3 , Hareesha Rishab Bharadwaj  4 , Nicholas Aderinto  5 , Joecelyn Kirani Tan  6 , Helen Ye Rim Huang  7 , Jeisun Poornaselvan  8 , Muhammad Hamza Shah  9 , Oday Atallah  10 , Aya Tawfik  11 , Mohamed Elsayed Abdelmeguid Elsayed Elmanzalawi  12 , Sama Hesham Ghozlan  13 , Toufik Abdul-Rahman  14 , Jeremiah Adepoju Moyondafoluwa  15 , Athanasios Alexiou  16   17   18   19 , Marios Papadakis  20
Affiliations
Review

Chromosomal instability: a key driver in glioma pathogenesis and progression

Adele Mazzoleni et al. Eur J Med Res. .

Abstract

Chromosomal instability (CIN) is a pivotal factor in gliomas, contributing to their complexity, progression, and therapeutic challenges. CIN, characterized by frequent genomic alterations during mitosis, leads to genetic abnormalities and impacts cellular functions. This instability results from various factors, including replication errors and toxic compounds. While CIN's role is well documented in cancers like ovarian cancer, its implications for gliomas are increasingly recognized. CIN influences glioma progression by affecting key oncological pathways, such as tumor suppressor genes (e.g., TP53), oncogenes (e.g., EGFR), and DNA repair mechanisms. It drives tumor evolution, promotes inflammatory signaling, and affects immune interactions, potentially leading to poor clinical outcomes and treatment resistance. This review examines CIN's impact on gliomas through a narrative approach, analyzing data from PubMed/Medline, EMBASE, the Cochrane Library, and Scopus. It highlights CIN's role across glioma subtypes, from adult glioblastomas and astrocytomas to pediatric oligodendrogliomas and astrocytomas. Key findings include CIN's effect on tumor heterogeneity and its potential as a biomarker for early detection and monitoring. Emerging therapies targeting CIN, such as those modulating tumor mutation burden and DNA damage response pathways, show promise but face challenges. The review underscores the need for integrated therapeutic strategies and improved bioinformatics tools like CINdex to advance understanding and treatment of gliomas. Future research should focus on combining CIN-targeted therapies with immune modulation and personalized medicine to enhance patient outcomes.

Keywords: Chromosomal instability; Gliomas; Molecular genetics; Neuro-oncology.

PubMed Disclaimer

Conflict of interest statement

The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Role of chromosomal instability in the development of early glioma. DNA: Deoxyribonucleic acid
Fig. 2
Fig. 2
Role of chromosomal aberrations in the progression of glioblastoma—IDH wildtype. glioblastoma multiforme, GBM; isocitrate dehydrogenase, IDH; epidermal growth factor receptor, EGFR; tumor protein p53, TP53; phosphatase and tensin homolog, PTEN; cyclin-dependent kinase inhibitor 2A, CDKN2A; retinoblastoma protein 1, RB1
Fig. 3
Fig. 3
Role of genetic dysregulation in astrocytomas with IDH mutation. IDH 1,2: isocitrate dehydrogenase 1,2. DNA: deoxyribonucleic acid. SAM: S-adenosine methionine. ATRX: ATRX (alpha-thalassemia/mental retardation, X-linked). TP 53: transformation-related protein 53
Fig. 4
Fig. 4
Role of chromosomal instability (CIN) in the pathogenesis of IDH-mutant oligodendroglioma. DNA: deoxyribonucleic acid. IDH: isocitrate dehydrogenase
Fig. 5
Fig. 5
Role of chromosomal instability in pediatric astrocytoma. ERK, extracellular signal regulated kinase; JNK, c-Jun N-terminal kinase; MEK, Mitogen-activated protein kinase kinase
See this image and copyright information in PMC

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