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Updated: Oct 27, 2025
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population
C B Westphalen1, M G Krebs2, C Le Tourneau3,4,5
1Comprehensive Cancer Center Munich & Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. cwestpha@med.lmu.de.
Abstract:
Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are rare oncogenic drivers in solid tumours. This study aimed to interrogate a large real-world database of comprehensive genomic profiling data to describe the genomic landscape and prevalence of NTRK gene fusions. NTRK fusion-positive tumours were identified from the FoundationCORE® database of >295,000 cancer patients. We investigated the prevalence and concomitant genomic landscape of NTRK fusions, predicted patient ancestry and compared the FoundationCORE cohort with entrectinib clinical trial cohorts (ALKA-372-001 [EudraCT 2012-000148-88]; STARTRK-1 [NCT02097810]; STARTRK-2 [NCT02568267]). Overall NTRK fusion-positive tumour prevalence was 0.30% among 45 cancers with 88 unique fusion partner pairs, of which 66% were previously unreported. Across all cases, prevalence was 0.28% and 1.34% in patients aged ≥18 and <18 years, respectively; prevalence was highest in patients <5 years (2.28%). The highest prevalence of NTRK fusions was observed in salivary gland tumours (2.62%). Presence of NTRK gene fusions did not correlate with other clinically actionable biomarkers; there was no co-occurrence with known oncogenic drivers in breast, or colorectal cancer (CRC). However, in CRC, NTRK fusion-positivity was associated with spontaneous microsatellite instability (MSI); in this MSI CRC subset, mutual exclusivity with BRAF mutations was observed. NTRK fusion-positive tumour types had similar frequencies in FoundationCORE and entrectinib clinical trials. NTRK gene fusion prevalence varied greatly by age, cancer type and histology. Interrogating large datasets drives better understanding of the characteristics of very rare molecular subgroups of cancer and allows identification of genomic patterns and previously unreported fusion partners not evident in smaller datasets.
Insights
Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are rare drivers in solid tumors. This study found NTRK fusions in 0.30% of cancers, with higher prevalence in younger patients and salivary gland tumors, revealing new fusion partners.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are oncogenic drivers in various solid tumors.
- Understanding their prevalence and genomic landscape is crucial for targeted therapies.
Purpose of the Study:
- To investigate the prevalence and genomic landscape of NTRK gene fusions in a large real-world cancer database.
- To compare findings with clinical trial cohorts and identify novel fusion partners.
Main Methods:
- Analysis of comprehensive genomic profiling data from the FoundationCORE® database (>295,000 patients).
- Identification and characterization of NTRK fusion-positive tumors.
- Comparison with entrectinib clinical trial data.
Main Results:
- NTRK fusions were identified in 0.30% of 45 cancer types, with 88 unique fusion partners (66% novel).
- Prevalence was higher in pediatric (<18 years, 1.34%) and very young (<5 years, 2.28%) patients, and in salivary gland tumors (2.62%).
- No correlation with other actionable biomarkers, except association with microsatellite instability (MSI) in colorectal cancer (CRC), with mutual exclusivity to BRAF mutations.
Conclusions:
- NTRK gene fusion prevalence varies significantly by age, cancer type, and histology.
- Large-scale data analysis is essential for characterizing rare molecular subgroups and discovering novel genomic patterns and fusion partners.
