Differences Among Genomic Profiling Tests for Bone and Soft-Tissue Sarcomas in a Universal Health Insurance System

BACKGROUND: Accurate identification of gene fusions is critical for precision oncological approaches to sarcomas, where specific fusion genes are actionable targets of tyrosine kinase (TK) inhibitors. This study provides a descriptive overview of the real-world use, under a universal health insurance program, of 3 different comprehensive genomic profiling (CGP) panels within the Japanese national CGP system: GenMineTOP, which integrates DNA and RNA sequencing, and 2 DNA-based panels, FoundationOne CDx and the OncoGuide NCC Oncopanel System. METHODS: We examined 2,633 sarcoma cases from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database to identify potentially actionable alterations classified by the Cancer Knowledge Database (CKDB). The mean patient age was 51.1 years, and 45% were female. Detection rates of TK fusions (FGFR1-4, NTRK1-3, ALK, RET, ROS1, and BRAF) were compared descriptively. Additionally, 3 sarcoma cases with an NTRK fusion detected by GenMineTOP were functionally validated. RESULTS: Potentially actionable alterations (CKDB Levels A, B, and C) were identified in 566 patients (21.5%). Actionable TK fusions were detected in 3.1% (8 of 254) with GenMineTOP, 1.4% (31 of 2,211) with FoundationOne CDx, and 0.6% (1 of 168) with NCC Oncopanel. GenMineTOP identified rare NTRK fusions, including RBPMS::NTRK2, HTT::NTRK2, and EML4::NTRK3. Functional assays suggested their oncogenic potential and demonstrated responsiveness to the TK inhibitors larotrectinib and entrectinib. CONCLUSIONS: In this cohort, the DNA+RNA-based panel showed a higher detection rate for TK fusions, although the panels were applied to different patient groups and the sensitivity and specificity could not be determined. Future studies evaluating different test types on the same tumor specimens are warranted to clarify whether the dual-sequencing approaches can improve the identification of actionable genetic events. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.