Impact of RNA sequencing on diagnosis and therapy: Early results from a tertiary cancer center in India.

Abstract

e23522 Background: RNA sequencing (RNA-seq) can detect gene fusions and expression-linked copy-number events that may be missed or remain ambiguous on standard workup. We evaluated the real-world clinical utility of RNA-seq specifically through fusion and amplification detection, focusing on whether results changed diagnosis and/or altered treatment. Methods: We reviewed consecutive patients undergoing RNA-seq at our center. Utility endpoints were captured prospectively/retrospectively in the dataset as (1) diagnosis change owing to RNA-seq and (2) treatment-course change owing to RNA-seq. For this analysis, RNA-seq “unique yield” was defined as fusion and/or amplification reported. Outcomes were summarized overall and by sarcoma/mesenchymal vs other cancers. Results: Among 26 evaluable patients, RNA-seq identified fusions and/or amplifications in 13/26 (50.0%) (fusions: 12/26 [46.2%]; amplifications: 3/26 [11.5%]). Diagnosis changed owing to RNA-seq in 4/26 (15.4%), and all diagnosis-changing cases were fusion-driven (4/4). Treatment-course change attributable to RNA-seq was documented in 6/25 (24.0%) patients with evaluable treatment-impact data. Fusion/amplification yield was higher in sarcoma/mesenchymal tumors (8/14 [57.1%]) than in other cancers (5/12 [41.7%]). Diagnosis change owing to RNA-seq occurred in 3/14 (21.4%) sarcoma/mesenchymal cases and 1/12 (8.3%) other cancers; treatment change owing to RNA-seq was observed in 3/13 (23.1%) vs 3/12 (25.0%), respectively. Conclusions: In this real-world cohort, RNA-seq demonstrated meaningful clinical utility primarily through fusion/amplification detection, with 15.4% diagnosis changes and 24.0% treatment changes attributable to RNA-seq. Impact was enriched in fusion/amplification-positive cases, supporting RNA-seq as a high-value adjunct test—particularly in diagnostically challenging sarcoma/mesenchymal tumors and selected carcinomas. Diagnosis change owing to RNA-seq (fusion-driven). Case Pre-RNA working diagnosis Histopathology Key RNA-seq finding (fusion/amp) Post-RNA integrated diagnosis / implication (as recorded) 1 Metastatic adenocarcinoma, CUP Adenocarcinoma FGFR–FILIP1 fusion Likely cholangiocarcinoma (site-of-origin reclassification) 2 Atypical teratoid / rhabdoid tumor ATRT, metastatic SS18–SSX2 fusion (t(18;X)) Fusion-consistent synovial sarcoma biology → diagnostic reclassification 3 Spindle cell tumor (low malignant potential; SMC differentiation) Spindle cell tumor (low malignant potential; SMC differentiation) LRRFIP1–ALK fusion ALK-rearranged IMT biology confirmed → diagnostic refinement/reclassification 4 Tenosynovial giant cell tumor (TGCT) Spindle cell tumor (intermediate malignant potential; myogenic differentiation) RRBP1–USP6 fusion Nodular fasciitis (benign) → diagnosis changed to benign entity