ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2019
Molecular characterization of cancers with NTRK gene fusions.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers, 5 of them syntheses that pooled it.
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Who cites it
227 citing papers in PubMed, 5 syntheses or guidelines pooled it, 477 citations in OpenAlex.
- SEOM-GECOD clinical guideline for cancer of unknown primary (update 2025).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Guideline
- Pooled it
- Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors.International journal of clinical oncology · 2023Guideline
- Comparison of Molecular Methods and BRAF Immunohistochemistry (VE1 Clone) for the Detection of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Meta-Analysis.Head and neck pathology · 2020Pooled it
- Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Guideline
- Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors.Neuro-oncology · 2022Trial
- Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma.Scientific reports · 2021Trial
- Immunohistochemistry as a screening tool for NTRK gene fusions: results of a first Belgian ring trial.Virchows Archiv : an international journal of pathology · 2021Trial
- Exosomal miR-145-5p inhibits papillary thyroid cancer by targetingOncology letters · 2026Article
- Not all NTRK fusions in mesenchymal neoplasia are driver events: implications on classification and targeted therapy.The journal of pathology. Clinical research · 2026Article
- Exploring the Impact of Multiple Gene Mutations on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Response in Asian Nonsmall Cell Lung Cancer Patients.ACS pharmacology & translational science · 2026Review
- Pan-TRK expression and NTRK gene aberrations in meningiomas: association with tumor grade and proliferative activity.The journal of pathology. Clinical research · 2026Article
- NTRK-rearranged uterine sarcomas with heterologous rhabdomyoblastic and cartilaginous differentiation: expanding the morphological spectrum with discussion of passenger NTRK molecular events.Virchows Archiv : an international journal of pathology · 2026Article
- Pathology-guided enrichment of targetable gene rearrangements in BRAF wild-type papillary thyroid carcinoma.Scientific reports · 2026Article
- TRK inhibitors in pediatric gliomas.Neuro-oncology advances · 2026Review
- Detection of NTRK gene fusions in sarcomas: a comparative study of Pan-TRK immunohistochemistry, FISH, and RNA-Based NGS.Pathologica · 2026Article
- Diagnostic and Therapeutic Strategies for Brain Metastases from Unknown Primary Tumors: A Comprehensive Review.Journal of clinical medicine · 2026Review
- Molecular landscape and biomarker associations of functionalTranslational cancer research · 2026Article
- MMTV-like Viruses and Human Breast Cancer: Evidence for Causality.Current issues in molecular biology · 2026Review
- Article
167 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted inhibitors of neurotropic tyrosine kinases are highly effective in selected patients with gene fusions involving NTRK1, NTRK2, or NTRK3. These fusions are consistently detected in rare cancer types (e.g., secretory breast carcinoma and congenital infantile fibrosarcoma), but the occurrence of NTRK fusions in common cancers and their relationship to other therapy biomarkers are largely unexplored. Tissue samples from 11,502 patients were analyzed for 53 gene fusions and sequencing of 592 genes, along with an immunohistochemical evaluation of TrkA/B/C and PD-L1. Thirty-one cases (0.27% of the entire cohort) had NTRK fusions. The most common fusions were ETV6:NTRK3 (n = 10) and TPM3:NTRK1 (n = 6). Gliomas had the highest number of NTRK fusions (14/982, 1.4%), most commonly involving NTRK2 (n = 9). Seventeen non-glioma cases with NTRK fusions included carcinomas of the lungs, thyroid, breast, cervix, colon, nasal cavity, cancer of unknown primary and soft tissue sarcomas. Strong and uniform Trk expression detected with a pan-Trk immunohistochemistry characterized 7/8 NTRK1 fusion cases and 8/9 NTRK2 fusion cases, while NTRK3 fused cases were positive in 6/11 (55%) of cases. 29% of NTRK fusion cases had no other pathogenic genomic alteration. PD-L1 expression was observed in 23% of NTRK fused cases while high tumor DNA microsatellite instability was detected in two cases. We confirm the rarity of NTRK genes fusions outside the brain malignancies. NTRK inhibitors alone or combined with immune checkpoint inhibitors may be a therapeutic option for a substantial proportion of these patients. Strategies for detection of the NTRK fusion-driven cancers may include immunohistochemistry, but gene fusion detection remains the most reliable tool.
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