The Application of Next Generation Sequencing in Gliomas: A Systematic Review of Diagnostic and Therapeutic Implications

Gliomas account for the vast majority of primary tumors that develop in the central nervous system. They represent one of the most aggressive and treatment-resistant types of brain tumors. Thus, early diagnosis and treatment are very important factors influencing outcome. Traditionally, the diagnosis of gliomas has been based on histopathological examination, imaging modalities, and the identification of biomarkers. Treatment options have primarily been centered on surgery, radiotherapy, and chemotherapies but their effectiveness is limited by the heterogeneous nature of gliomas and their resistance to standard therapies. The emergence of Next-Generation Sequencing (NGS) has been utilized as a valuable tool for assessing the molecular heterogeneity of gliomas and characterizing their genetic profile in recent years, which can lead to better diagnostic and therapeutic decision-making approaches. This review systematically assesses the impact of NGS on glioma diagnosis and treatment. Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science databases to from ۲۰۱۴ up to August ۲۰۲۴ using related MeSH and free-text terms. Duplicates were eliminated by Endnote software and titles and abstracts were screened. Eligibility criteria included clinical trial studies (Phase I, II, III, or IV) which applied NGS in patients with different types of glioma for diagnosis, prognosis, or treatment or trials applying NGS for identifying relevant genetic mutations, or biomarker discovery. Two independent reviewers screened the remaining articles and conflicts were resolved by a third reviewer. Relevant English peer-reviewed articles were included and animal studies, observational studies, case studies, preclinical research, editorials, reviews, and book chapters were excluded. Demanded data were extracted into a Microsoft Excel spreadsheet. The data extraction process relied on the clinical information provided, diagnostic accuracy, and recent therapeutic options or outcomes through NGS regarding patient survival, tumor response, or recurrence. Microsoft Excel sheet was used for data extraction. Quality assessment was performed using JBI’s critical appraisal tool. Results: The initial search retrieved ۳,۵۶۰ articles which was reduced to ۲۷۰۱ after eliminating the duplicates. Eight studies met the criteria of the systematic review and were included in the final analysis. NGS technologies have improved accuracy and precision of glioma diagnoses highlighting the significant genetic changes such as mutations in IDH۱/۲, and BRAF promoter alterations, and the eventual identification of molecular subtypes of glioma. NGS has more importantly suggested potential personalized treatment options considering various mutations with sensitivity/resistance to other treatment options. Challenges remain for implementation of NGS findings into standardized clinical practice including cost and interpretation. Conclusion: Characteristic genetic profiles have been identified to have diagnostic and prognostic predictive potential in glioma. In the included studies, NGS as a promising diagnostic technique, has been utilized for molecular classification of tumors into biological groups based on the most frequently altered genes in glioma including: IDH ½, BRAF, etc. Application of NGS in the studies had led to better patient outcomes, reflecting the value of NGS to match selected therapy with genomic alterations of patients. Thus, further studies are required to review the limitations in clinical implementation in order to improve clinical care outcomes.

کلیدواژه ها:

Next Generation Sequencing ، Glioma ، Genetic mutations