Abstract 5326: High throughput genomic profiling of tissue and liquid biopsy samples reveals targetable mutations in NSCLC patients from the Indian population.

Abstract Background: Non-Small Cell Lung Cancer (NSCLC), accounts for approximately 85% of lung cancer cases and ranking as the foremost cause of cancer related deaths globally, is both highly aggressive and uniquely characterized by the broadest spectrum of approved targeted treatments. Comprehensive genomic profiling (CGP) using next-generation sequencing (NGS) has become integral to clinical practice, with tissue and plasma-based analysis of cell free circulating tumor DNA (ctDNA) representing the most established and widely adopted modality in NSCLC. Addressing the scarcity of molecular data in Indian NSCLC patients, this study aims to delineate the mutational spectrum through NGS based profiling of FFPE and plasma ctDNA samples, driving advances in targeted therapy and precision medicine. Methods: The study included 45 FFPE tissue and plasma specimens from NSCLC patients, enabling a robust comparison of solid and liquid biopsy approaches. Comprehensive genomic profiling was performed on a total of 45 samples using the G2M PanCan CGP assay, which targets 681 clinically relevant genes with approximately 1.7 Mb of genomic regions and was sequenced on the Illumina platform. Bioinformatics analysis was conducted using the GATK v4.1.2 somatic variant calling pipeline, and downstream visualization of mutational landscapes and hotspot regions was achieved using MAF tools. Results: Consistent mutations were detected in both FFPE tissue and plasma ctDNA samples, with prominent alterations in TP53 showing the highest frequency and clinical relevance, accompanied by alterations in EGFR, ASXL1 and ARID1A. With variant allele frequencies of 6-39% in FFPE and 0.9-3.0% in liquid biopsy samples, the assay proved effective across sample types, producing a highly concordant mutational profile. TP53 was the most frequently mutated gene, exhibiting hotspot variants such as G325, P152L, H179D, and L194R, underscoring its critical role in NSCLC pathogenesis. Conclusions: By mapping mutations in key NSCLC associated genes, the investigation confirms that NGS-based comprehensive genomic profiling delivers reliable and concordant detection across FFPE tissue and plasma ctDNA samples. This finding highlights the assay’s utility for integrating tissue and liquid biopsy into routine clinical practice, empowering clinicians with accurate genomic insights to guide targeted mutation driven therapy decisions. Citation Format: Amit Kumar, Puja Sinha, Rama Chandran, Shobit Gupta, Giulliana Tessarin. High throughput genomic profiling of tissue and liquid biopsy samples reveals targetable mutations in NSCLC patients from the Indian population abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5326.