Unveiling Actionable Pathogenic Genes for Precision Oncology in Brain Cancers: Glioblastoma and Astrocytoma

Open Access

Year : 2026 | Volume : 15 | Issue : 02 | Page : 43 59
By

Amrutha R. Kenche,

Sasivarman Selvam,

Sailee Prakash Hingane,

Deepthi Pilli,

Taiba Shamim,

Aarya Senan T. S,

Palak Vyas,

Sanika Durgavali,

1. Doctoral Student, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
2. Junior Bioinformation, SyncBio Technologies, Ashok Nagar, Lawspet, Puducherry, India
3. Independent researcher, Pune, Maharashtra, India
4. NGS Research Intern, Department of Biotechnology, Kakatiya University, Warangal, Telangana, India
5. Students, Department of Computer Science, Jamia Millia Islamia, New Delhi, Delhi, India
6. Independent Researcher (Senior Genome Analyst),Bangalore, India
7. Student, Department of Biotechnology, Mahila P.G. Mahavidyalaya (Affiliated to J.N.V.U.), Jodhpur, Rajasthan, India
8. Student, Department of Biotechnology, The Institute of Science, Mumbai, Maharashtra, India

Abstract

Glioblastoma (GBM) and astrocytoma are aggressive primary brain tumors characterized by significant molecular heterogeneity, complicating effective treatment. This study employed targeted next-generation sequencing of 529 cancer-associated genes on matched tumor-normal pairs from GBM and astrocytoma patients. Somatic variants were identified using a rigorous bioinformatic pipeline adhering to GATK Best Practices, with variant allele frequencies (VAF) calculated to assess clonal dominance. Functional annotation and driver mutation classification were performed using Ensemble Variant Effect Predictor and Cancer Genome Interpreter. The clinical actionability of identified mutations was evaluated based on the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). In the GBM sample, dominant near-clonal driver mutations were identified in EGFR (p.Asp256Ala; VAF = 0.976) and TP53 (p.Arg175His; VAF = 0.788), implicating proliferative signaling and tumor suppressor disruption. The astrocytoma sample exhibited hallmark driver mutations in IDH1 (p.Arg132His; VAF=0.601) and ATRX (frameshift deletion; VAF = 0.932), consistent with metabolic reprogramming and chromatin remodeling. Several additional high-confidence somatic drivers were detected, representing viable therapeutic targets. These findings align with ESCAT Tier 1/2 alterations, supporting their potential for molecularly matched therapies. The identification of distinct, actionable somatic drivers in GBM and astrocytoma underscores the critical importance of molecular stratification in neuro-oncology. This approach facilitates a shift from uniform treatment paradigms toward biomarker-driven precision medicine, promising improved patient stratification and targeted therapeutic interventions.

Keywords: Glioblastoma, astrocytoma, somatic mutations, EGFR, TP53, IDH1, ATRX, precision oncology, targeted therapy, molecular stratification

[This article belongs to Research and Reviews : Journal of Computational Biology ]

How to cite this article: Amrutha R. Kenche, Sasivarman Selvam, Sailee Prakash Hingane, Deepthi Pilli, Taiba Shamim, Aarya Senan T. S, Palak Vyas, Sanika Durgavali. Unveiling Actionable Pathogenic Genes for Precision Oncology in Brain Cancers: Glioblastoma and Astrocytoma. Research and Reviews : Journal of Computational Biology. 2026; 15(02):43-59.
How to cite this URL: Amrutha R. Kenche, Sasivarman Selvam, Sailee Prakash Hingane, Deepthi Pilli, Taiba Shamim, Aarya Senan T. S, Palak Vyas, Sanika Durgavali. Unveiling Actionable Pathogenic Genes for Precision Oncology in Brain Cancers: Glioblastoma and Astrocytoma. Research and Reviews : Journal of Computational Biology. 2026; 15(02):43-59. Available from: https://journals.stmjournals.com/rrjocb/article=2026/view=255259

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Regular Issue Open Access Original Research
Volume 15
Issue 02
Received 26/08/2026
Accepted 02/09/2026
Published 11/09/2026
Publication Time 16 Days

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