Related Experiment Video
Updated: May 29, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Differences Among Genomic Profiling Tests for Bone and Soft-Tissue Sarcomas in a Universal Health Insurance System
Satoshi Kamio1,2, Masachika Ikegami1, Rina Kitada1
1Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.
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.
Insights
A DNA+RNA comprehensive genomic profiling panel detected more tyrosine kinase (TK) fusions in sarcomas than DNA-only panels. This dual-sequencing approach identified actionable NTRK fusions responsive to targeted therapies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Accurate gene fusion identification is crucial for precision oncology in sarcomas.
- Specific gene fusions are actionable targets for tyrosine kinase (TK) inhibitors.
- This study evaluates three comprehensive genomic profiling (CGP) panels used in Japan.
Purpose of the Study:
- To descriptively overview the real-world use of three CGP panels in Japan.
- To compare the detection rates of actionable TK fusions across different CGP panels.
- To functionally validate identified NTRK fusions.
Main Methods:
- Examined 2,633 sarcoma cases from the C-CAT database.
- Identified potentially actionable alterations using the Cancer Knowledge Database (CKDB).
- Compared detection rates of TK fusions (FGFR, NTRK, ALK, RET, ROS1, BRAF) across GenMineTOP (DNA+RNA), FoundationOne CDx (DNA), and NCC Oncopanel (DNA).
Main Results:
- Potentially actionable alterations were found in 21.5% of patients.
- The DNA+RNA panel (GenMineTOP) detected TK fusions at a higher rate (3.1%) compared to DNA-only panels (1.4% and 0.6%).
- GenMineTOP identified rare NTRK fusions, which showed oncogenic potential and sensitivity to TK inhibitors in functional assays.
Conclusions:
- The DNA+RNA-based panel demonstrated a higher detection rate for TK fusions in sarcomas.
- While the study provides valuable real-world data, sensitivity and specificity could not be determined due to different patient groups.
- Further studies comparing different test types on identical tumor specimens are needed to confirm the benefits of dual-sequencing approaches.
