Genomic profiling of Indian gliomas reveals mutually exclusive IDH1 mutations and EGFR amplifications with distinct grade and age association and clinical implications

Objectives: Gliomas are the most prevalent glial-derived primary tumours of the central nervous system (CNS) with a complex and heterogeneous landscape. While global genomic studies have shaped glioma classification and management, data from Indian populations remain sparse. Understanding population-specific molecular alterations is essential to guide precision oncology efforts in diverse settings. Material and Methods: We analysed 37 Indian glioma samples using the Oncomine Dx Express Test (ODxET TM ), a next-generation sequencing (NGS) panel covering 46 cancer-associated genes. Findings were validated against public glioma datasets (MSK-IMPACT and FMI from cBioPortal). Results: Oncogenic or likely-oncogenic alterations were identified in 35 samples across 24 genes. Frequent alterations included TP53 and IDH1 (48.6%), EGFR (40.5%), RET (29.7%), and PIK3CA (27.0%). EGFR amplifications (14.9%) were mutually exclusive with IDH1 mutations and observed predominantly in Grade IV gliomas and older patients. IDH1 mutations were enriched in lower-grade gliomas (Grades II–III, 80.9%). EGFR alterations co-occurred with CDKN2A/B, TERT, and PTEN, while IDH1 mutations were associated with ATRX, TP53, CIC, and FUBP1. Clinically actionable variants were identified in 81.1% of cases, with 45.9% classified as level 3A (OncoKB). IDH1 p.R132 was the most frequent actionable mutation. Conclusion: This study highlights the distinct molecular subtypes of Indian gliomas, particularly IDH1-mutant and EGFR-amplified tumours, and their association with histological grade and age. Our findings underscore the value of incorporating molecular profiling into routine clinical care to inform targeted therapy and guide future research in Indian glioma patients.