Comprehensive Genomic Profiling Across Diverse Tumors Using the OncoIndx® Assay: Real-World Insights From an Indian Cohort.

Background Comprehensive genomic profiling (CGP) enables the simultaneous detection of actionable genomic alterations and predictive biomarkers across diverse malignancies. However, real-world molecular oncology data from Indian populations remain limited. This study aimed to characterize the genomic landscape of diverse solid tumors using the OncoIndx® (OneCell Diagnostics India Pvt. Ltd., Mumbai, India) CGP platform within routine Indian clinical practice. Methods This retrospective single-center study included patients with histologically confirmed malignancies who underwent CGP testing between June 2022 and July 2025. Genomic profiling was performed using the OncoIndx® 1080-gene next-generation sequencing (NGS) platform, with analyses focused on mutation frequency, alteration type, pathway enrichment, clinical-actionability categorization, and exploratory biomarkers including microsatellite instability (MSI), tumor mutational burden (TMB), homologous recombination deficiency (HRD), programmed death-ligand 1 (PD-L1) expression, and circulating tumor DNA (ctDNA) tumor fraction. Results The cohort comprised 39 samples representing diverse solid tumors, predominantly gynecological, gastrointestinal, breast, central nervous system (CNS), and thoracic malignancies. A total of 124 genomic alterations involving 69 unique genes were identified in 33 patients, while six patients demonstrated no detectable genomic alterations. TP53 was the most frequently altered gene (43.6%), followed by PIK3CA (17.9%), ATM (10.3%), and KRAS (10.3%). Category-wise analysis demonstrated substantial clinical relevance, with Categories 1 and 2 collectively accounting for 47.6% of all detected alterations. Pathway enrichment analysis revealed predominant involvement of TP53/cell-cycle (24.2%), PI3K/AKT/mTOR (15.3%), DNA damage repair/HRD-homologous recombination repair (HRD-HRR) (12.9%), and RTK/RAS/MAPK signaling pathways (9.7%). Somatic mutation mapping demonstrated marked inter-patient molecular heterogeneity, encompassing missense mutations, amplifications, frameshift variants, splice-site alterations, and fusion events. Exploratory biomarker analysis revealed predominantly low MSI and low TMB, although isolated MSI-high, elevated TMB, and HRD-positive tumors were identified. Variable concordance between tissue biopsy- and liquid biopsy-based PD-L1 assessment further underscored underlying tumor heterogeneity. Conclusions This real-world Indian cohort demonstrated extensive genomic heterogeneity across diverse solid tumors, with recurrent alterations involving TP53/cell-cycle, PI3K/AKT/mTOR, DNA damage repair, and RTK/RAS/MAPK pathways. OncoIndx®-based CGP enabled the broad molecular characterization and identification of clinically relevant genomic alterations and exploratory biomarkers. These findings provide descriptive real-world molecular insights from an underrepresented Indian population and support further prospective evaluation of the clinical utility and outcome implications of CGP in Indian oncology practice.