Radiation-induced gliomas: a report of four cases and analysis of molecular biomarkers
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Updated: Feb 24, 2026
Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Tsunehito Nakao1, Yasuo Sasagawa2, Sumihito Nobusawa3
1Division of Neuroscience, Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
Abstract:
Radiation-induced glioma (RIG) is a rare secondary glioma. The tumors morphologically resemble their sporadically arising counterparts. Recently, the WHO classification of tumors of the central nervous system was revised to incorporate molecular biomarkers together with classic histological features. The status of molecular biomarkers in RIG, however, remains unclear. The objective of this study was to investigate if commonly accepted glioma-specific biomarkers are relevant in RIGs. Among 269 gliomas diagnosed as WHO grade 2, 3 and 4 in our institution, four were diagnosed as RIGs. Immunohistochemical (IHC) staining for isocitrate dehydrogenase 1 (IDH1), p53, alpha thalassemia/mental retardation syndrome X-linked (ATRX), and H3K27M, and direct DNA sequencing of IDH1/2, telomerase reverse transcriptase (TERT) promoter, Histone H3.3 (H3F3A) and B-Raf (BRAF) genes was performed. All tumor specimens were IDH1-, p53- and H3K27M-negative. The nuclei of tumor cells in all cases exhibited positive staining for ATRX. In direct DNA sequencing analysis, no IDH1, IDH2, TERT promoter, H3F3A or BRAF mutations were found in any of the cases. Our findings suggest that these characteristic glioma-associated molecular mutations may be rare events in RIGs. More RIGs need to be tested for analysis of molecular biomarkers to clarify the clinical and histopathological spectra of this tumor.
Insights
Radiation-induced gliomas (RIGs) rarely show common molecular biomarkers. This study found no IDH1/2, TERT, H3F3A, or BRAF mutations in four RIG cases, suggesting these markers are not typical for RIGs.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Radiation Oncology
Background:
- Radiation-induced glioma (RIG) is a rare secondary brain tumor.
- WHO classification now integrates molecular biomarkers with histology for CNS tumors.
- The molecular profile of RIGs remains largely uncharacterized.
Observation:
- This study analyzed four RIG cases for common glioma biomarkers.
- Immunohistochemistry and DNA sequencing were used to assess IDH1, p53, ATRX, H3K27M, IDH1/2, TERT promoter, H3F3A, and BRAF.
- All RIGs were negative for IDH1, p53, and H3K27M, but positive for ATRX.
Findings:
- No mutations in IDH1, IDH2, TERT promoter, H3F3A, or BRAF genes were detected in the RIG samples.
- These findings indicate that typical glioma-associated molecular alterations are infrequent in radiation-induced gliomas.
Implications:
- The molecular landscape of RIGs differs from sporadic gliomas.
- Further research with larger cohorts is needed to fully elucidate RIG molecular biomarkers.
- Understanding RIG molecular characteristics is crucial for diagnosis and potential targeted therapies.
