Chromosomal instability: a key driver in glioma pathogenesis and progression

Abstract

Chromosomal instability (CIN) is a pivotal factor in gliomas, contributing to their complexity, progression, and thera‑ peutic challenges. CIN, characterized by frequent genomic alterations during mitosis, leads to genetic abnormali‑ ties 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 infuences glioma progression by afecting key oncological pathways, such as tumor sup‑ pressor genes (e.g., TP53), oncogenes (e.g., EGFR), and DNA repair mechanisms. It drives tumor evolution, promotes infammatory signaling, and afects 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 Pub‑ Med/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 fndings include CIN’s efect on tumor heterogeneity and its potential as a biomarker for early detection and monitoring. Emerging therapies tar‑ geting 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 bioinfor‑ matics tools like CINdex to advance understanding and treatment of gliomas. Future research should focus on com‑ bining CIN-targeted therapies with immune modulation and personalized medicine to enhance patient outcomes.