Abstract
Purpose
Molecular Profiling of solid tumours is extensively used for prognostic, theranostic, and risk prediction. Next generation sequencing (NGS) has emerged as powerful method for molecular profiling. The present study was performed to identify molecular alterations present in solid tumours in Indian tertiary cancer centre.
Methods
Study included 1140 formalin Fixed paraffin embedded samples. NGS was performed using two targeted gene panels viz. Ampliseq Focus panel and Sophia Solid Tumor Plus Solution. Data was analyzed using Illumina’s Local Run Manager and SOPHiA DDM software. Variant interpretation and annotations were done as per AMP/ACMG guidelines.
Results
Total 896 cases were subjected to NGS after excluding cases with suboptimal nucleic acid quality/quantity. DNA alterations were detected in 64.9% and RNA fusions in 6.9% cases. Among detected variants, 86.7% were clinically relevant aberrations. Mutation frequency among different solid tumours was 70.8%, 67.4%, 64.4% in non-small cell lung (NSCLC), lung squamous cell carcinomas and head neck tumours respectively. EGFR, KRAS, BRAF, ALK and ROS1were commonly altered in NSCLC. Gastrointestinal tumours showed mutations in 63.6% with predominant alterations in pancreatic (88.2%), GIST (87.5%), colorectal (78.7%), cholangiocarcinoma (52.9%), neuroendocrine (45.5%), gall bladder (36.7%) and gastric adenocarcinomas (16.7%). The key genes affected were KRAS, NRAS, BRAF and PIK3CA. NGS evaluation identified co-occurring alterations in 37.7% cases otherwise missed by conventional assays. Resistance mutations were detected in progressive lung tumours (39.5%) against EGFR TKIs and ALK/ROS inhibitors.
Conclusion
This is the largest Indian study on molecular profiling of solid tumours providing extensive information about mutational signatures using NGS.
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Data availability
All data generated and analysed during this study are included in this published article [and its supplementary information files].
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Acknowledgements
The authors wish to acknowledge Mr. Sandeep Dhanavade, Mrs. RachnaRumde for their technical support in performing Fluorescent in situ hybridization and nucleic acid quality checks.
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Conceptualization: OS, SE, MG. Investigation: MG, PG, OS. Formal Analysis: MG, PG, OS, TP, GDNK, SE. Writing-original draft preparation and data analysis: MG, OS, TP. Writing-Review & editing: MG, OS, TP, SE, SD.
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Gurav, M., Epari, S., Gogte, P. et al. Targeted molecular profiling of solid tumours-Indian tertiary cancer centre experience. J Cancer Res Clin Oncol 149, 7413–7425 (2023). https://doi.org/10.1007/s00432-023-04693-3
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DOI: https://doi.org/10.1007/s00432-023-04693-3