DNA methylation in glioma: clinical biomarkers and emerging biosensor-based diagnostics
5 affiliations
- 1College of Medicine, Alfaisal University
- 2King Faisal Specialist Hospital and Research Centre
- 3Faculty of Medicine, Wroclaw Medical University
- 4School of Medicine, St. George’s University
- 5King Faisal Specialist Hospital and Research Center
Abstract
Gliomas are the most common malignant primary tumors of the central nervous system (CNS) and are characterized by marked molecular heterogeneity, aggressive clinical behavior, and poor patient outcomes. Among the epigenetic alterations implicated in glioma pathogenesis, DNA methylation has emerged as a key regulatory mechanism with important diagnostic, prognostic, and predictive value. Clinically established biomarkers, including O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and the glioma CpG island methylator phenotype (G-CIMP), have transformed patient stratification and therapeutic decision-making, while additional methylation signatures continue to expand the molecular classification of glioma. Conventional methylation detection methods, although highly accurate, remain limited by their cost, complexity, and dependence on specialized laboratory infrastructure. This review summarizes current knowledge of DNA methylation biology in glioma, discusses established and emerging methylation biomarkers, and critically examines recent advances in biosensor-based detection technologies, including electrochemical, optical, microfluidic, and nanopore-based platforms, together with enzyme-assisted and immunoaffinity-based molecular recognition strategies that can be combined with these transducers. These technologies, particularly when combined with nanomaterials, signal amplification strategies, and liquid biopsy approaches, offer highly sensitive, rapid, and minimally invasive detection of methylated circulating tumor DNA, supporting the development of point-of-care diagnostics. Despite encouraging progress, challenges related to analytical standardization, tumor heterogeneity, cross-reactivity, large-scale clinical validation, and regulatory translation remain significant barriers to routine implementation. By integrating recent advances in glioma epigenetics with emerging biosensing technologies, this review provides a comprehensive overview of the current landscape and highlights future opportunities for translating DNA methylation biomarkers into clinically accessible precision diagnostic platforms.
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BibTeX
@article{jabri2026methylation,
title = {{DNA methylation in glioma: clinical biomarkers and emerging biosensor-based diagnostics}},
author = {Abdullah Jabri and Shamsa Hilal Saleh and Mohamed Alsharif and Abdulfatah Hamouch and Juman Alammar and Hamidreza Emadzadeh and Raja Chinnappan and Ahmed Yaqinuddin and Mohammed Imran Khan},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1965742},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1965742/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - DNA methylation in glioma: clinical biomarkers and emerging biosensor-based diagnostics
AU - Abdullah Jabri
AU - Shamsa Hilal Saleh
AU - Mohamed Alsharif
AU - Abdulfatah Hamouch
AU - Juman Alammar
AU - Hamidreza Emadzadeh
AU - Raja Chinnappan
AU - Ahmed Yaqinuddin
AU - Mohammed Imran Khan
PY - 2026
DA - 2026/10/19
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1965742
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1965742/full
AB - Gliomas are the most common malignant primary tumors of the central nervous system (CNS) and are characterized by marked molecular heterogeneity, aggressive clinical behavior, and poor patient outcomes. Among the epigenetic alterations implicated in glioma pathogenesis, DNA methylation has emerged as a key regulatory mechanism with important diagnostic, prognostic, and predictive value. Clinically established biomarkers, including O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and the glioma CpG island methylator phenotype (G-CIMP), have transformed patient stratification and therapeutic decision-making, while additional methylation signatures continue to expand the molecular classification of glioma. Conventional methylation detection methods, although highly accurate, remain limited by their cost, complexity, and dependence on specialized laboratory infrastructure. This review summarizes current knowledge of DNA methylation biology in glioma, discusses established and emerging methylation biomarkers, and critically examines recent advances in biosensor-based detection technologies, including electrochemical, optical, microfluidic, and nanopore-based platforms, together with enzyme-assisted and immunoaffinity-based molecular recognition strategies that can be combined with these transducers. These technologies, particularly when combined with nanomaterials, signal amplification strategies, and liquid biopsy approaches, offer highly sensitive, rapid, and minimally invasive detection of methylated circulating tumor DNA, supporting the development of point-of-care diagnostics. Despite encouraging progress, challenges related to analytical standardization, tumor heterogeneity, cross-reactivity, large-scale clinical validation, and regulatory translation remain significant barriers to routine implementation. By integrating recent advances in glioma epigenetics with emerging biosensing technologies, this review provides a comprehensive overview of the current landscape and highlights future opportunities for translating DNA methylation biomarkers into clinically accessible precision diagnostic platforms.
SN - 2234-943X
ER -