Abstract 713: Utility of next generation sequencing multigene assay for comprehensive molecular profiling and targeted therapy in solid organ malignancies - An Indian experience

Abstract Introduction: Next-generation sequencing (NGS) has paved its path and broaden its utility in oncology practice. The dependability, experiments, pipeline building, data annotation, and its interpretation, including the cost have significantly improved in the recent years making its application more universal. As a result, molecular pathology is now essential for making treatment decisions in clinical practice as predictive and prognostic tools. The need of the hour is to identify a reliable and cost effective comprehensive genomic panel which can aid in a) massive parallel sequencing and screening of multiple genes at the same time; b) identifying deleterious somatic aberrations; c) assessing baseline disease progression / recurrence and guidance to therapy; d) conclude druggable tumor specific somatic mutations. This study aims at the validation and implementation of a comprehensive NGS panel in solid tumors. Methodology: A total of 243 patient samples (Females: 126, Males 117) were included. DNA and RNA were isolated from the tumor sample and subjected to target amplification using an optimized 161 gene panel (Oncomine Somatic 161 Gene Panel and Thermo Fischer Scientific Ion S5™ System). The NGS output sequences of the multigene assay were aligned to the human reference genome hg19 (GRCh37). The alignments and variant calling was done using the ION S5 torrent server. Variants were identified and interpreted using Ion Reporter Software. Results: The DNA and RNA alterations were more prevalent between 51-60 years in females, while 61-70 years in males. Total positivity rate was found to be 66% in males and 79% in females. The most prevalent mutations observed amongst females were TP53 (39% in lung cancers), KRAS (16% in lung cancers), PIK3CA (10% in breast cancers), NRAS (3% not specific to any particular cancer), CTNNB1 (3% not specific to particular cancer) and ATM (3% in pancreas cancers) while male preponderance were observed with EGFR (7% in lung cancers), CNVs (6% in stomach cancers), RB1 (3% in gall bladder cancers) and BRAF (3% in lung cancers). Conclusions: The study is unique as it allows thorough genetic profile of individuals by examining 161 genes at the same time, eliminating the need for several tests. The assay aids clinicians in personalizing drug regimens by understanding tumorigenic pathways and timely management of the disease. Comprehensive genomic profiling improves the evaluation of moderate/low penetration genes that are frequently overlooked in clinical genetic settings, resulting in a direct influence on providing individuals with appropriate genetic counselling and clinical care Keywords: NGS, 161 genes, Comprehensive molecular profiling Citation Format: Rahul Katara, Aditi Agarwal, Deepak K. Sharma, Vipin Kumar, Sagar S. Mohanty, Arti Yadav, Shivani Sharma, Mallika Dixit, Samriti Arora, Sambit K. Mohanty. Utility of next generation sequencing multigene assay for comprehensive molecular profiling and targeted therapy in solid organ malignancies - An Indian experience [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 713.