Abstract 3385: Real-world data analysis of somatic mutations using the GenMineTOP, a dual-targeted DNA and RNA comprehensive genomic profiling panel

Abstract Introduction: In Japan, comprehensive genomic profiling (CGP) tests have been covered by insurance since 2019, and the dual-targeted DNA and RNA CGP panel, GenMineTOP, has been covered since 2023. Of the CGP tests conducted under insurance, 99.6% of cases are registered in the nationwide database: Center for Cancer Genomics and Advanced Therapeutics (C-CAT). This study aims to elucidate somatic genomic alterations detected by GenMineTOP using real-world data from C-CAT. Method: We analyzed 1, 356 cases of GenMineTOP registered in the C-CAT database by June 2024. Clinical significance was determined based on the evidence level defined by C-CAT. We examined DNA mutations, copy number alterations, fusion/exon skipping, and TMB-high cases. Additionally, we performed multivariate analysis to assess the impact of DNA mutations, copy number amplifications, fusion genes, and primary organ on RNA expression levels. Results: The top five cancer types were bowel (15.4%), soft tissue (11.6%), CNS/brain (11.1%), pancreas (8.3%), and head and neck (5.6%). Oncogenic DNA mutations, copy number amplifications, and fusion/exon skipping were found in 1, 140, 342, and 117 cases, respectively. Fusion/exon skipping was more common in cases without DNA mutations (68/1140 vs. 49/216). Frequent DNA mutations included TP53, KRAS, APC, PIK3CA, and TERT. Copy number amplifications were most common in MDM2, CDK4, MYC, EGFR, and CCND1. TMB-high was observed in 72 cases (5.3%). The RNA panel detected 105 fusion cases and 13 exon skipping cases; 17 fusions were evidence level A (Japan- or FDA-approved drug for the cancer type) and 39 were diagnostically significant. NTRK fusions were detected in 11 cases (0.8%). Exon skipping was observed in EGFR (exon 2-7, n=5), CTNNB1 (exon 3, n=7), and ERBB2 (exon 16, n=1). Gene expression was influenced by the primary organ and the presence of gene amplification, fusion genes, and/or mutations. All 27 analyzed genes showed differences in expression depending on the primary organ, with ALK, NTRK2, and NTRK3 exhibiting particularly significant variations. These genes had the highest expression levels in the CNS/brain. The effect of gene amplification on expression levels varied by gene, with the most significant impact observed in CDK4 and MDM2. Mutations in KIT and TERT were linked to increased expression. Statistically significant overexpression was observed in cases positive for ALK, FGFR3, NTRK1, NTRK3, and RET fusions. Conclusion: GenMineTOP detected clinically significant fusion/exon skipping. Factors affecting RNA expression were quantitatively elucidated. Citation Format: Kousuke Watanabe, Miho Ogawa, Eri Habano, Aya Shinozaki-Ushiku, Masakazu Akahori, Toshimitsu Ichijo, Shuichi Tsutsumi, Kenji Tatsuno, Hiroyuki Aburatani, Hidenori Kage, Katsutoshi Oda. Real-world data analysis of somatic mutations using the GenMineTOP, a dual-targeted DNA and RNA comprehensive genomic profiling panel [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 3385.