NTRK1/2/3 gene fusion
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-NTRK-FUSION |
|---|---|
| Type | Biomarker |
| Aliases | ETV6-NTRK3LMNA-NTRK1NTRK rearrangementTRK fusionФузія генів NTRK1/2/3 |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 SRC-ONCOKB |
Biomarker Facts
| Biomarker type | gene_fusion |
|---|---|
| Mutation details | {"functional_impact": "Constitutive TRK kinase activity through 5'-partner-driven dimerization", "gene": "NTRK1 / NTRK2 / NTRK3", "gene_hugo_id": "HGNC:8031 (NTRK1) / HGNC:8032 (NTRK2) / HGNC:8033 (NTRK3)", "hotspots": ["ETV6-NTRK3 (canonical secretory carcinoma fusion — salivary MASC, infantile fibrosarcoma, secretory breast)", "LMNA-NTRK1 (soft-tissue / GI tumors)", "TPM3-NTRK1", "QKI-NTRK2 (pediatric glioma)", "BCAN-NTRK1 (pediatric glioma)"], "variant_type": "chromosomal rearrangement / fus... |
| Measurement | MethodRNA-based NGS (preferred, captures partners) OR pan-TRK IHC (screening) OR FISH break-apart (per gene) OR DNA-NGS with fusion-aware caller Unitscategorical (positive/negative); fusion partner + breakpoints reported Sensitivity requirementPan-TRK IHC ≥1+ → confirm by RNA-NGS or FISH; IHC less sensitive for NTRK3 fusions |
| Related biomarkers | None declared |
Notes
Tumor-agnostic FDA approval for larotrectinib (NAVIGATE / SCOUT) and entrectinib (STARTRK-1/2 + ALKA) for NTRK-fusion-positive solid tumors after progression or where no satisfactory alternative exists. Fusion frequency: ~0.3% of common adult tumors but >90% in rare entities — secretory carcinoma of salivary gland (MASC), infantile fibrosarcoma, congenital mesoblastic nephroma, secretory breast carcinoma. Pan-TRK IHC is a reasonable inexpensive screen but RNA-NGS remains the gold standard. Resistance: solvent-front (G595R, G623R) and gatekeeper (F589L) mutations on progression — selitrectinib / repotrectinib in development.
Used By
Actionability
BMA-NTRK-ETV6-SALIVARY- ETV6-NTRK3 is the defining fusion of mammary analogue secretory carcinoma (MASC) of saliv...BMA-NTRK-FUSION-CRC- NTRK fusion in CRC is rare (~0.1-0.3%) but enriched in MSI-H / Lynch syndrome CRC (~5-10%...BMA-NTRK-FUSION-GIST- NTRK fusion in GIST is rare and confined to KIT/PDGFRA wild-type GIST (which is itself ~1...BMA-NTRK-FUSION-IFS- Infantile fibrosarcoma (IFS) is defined by ETV6-NTRK3 fusion (>90%). Larotrectinib has tr...BMA-NTRK-FUSION-NSCLC- NTRK fusion in NSCLC is rare (~0.1-0.5%). Larotrectinib and entrectinib are FDA tumor-agn...BMA-NTRK-FUSION-SALIVARY- NTRK fusion in salivary gland tumors — virtually 100% of mammary analogue secretory carci...BMA-NTRK-FUSION-THYROID-PAPILLARY- NTRK fusion in papillary thyroid carcinoma (~1-2% sporadic, higher in radiation-induced d...
Algorithms
ALGO-IFS-1L- ALGO-IFS-1L
Diseases
DIS-IFS- Infantile fibrosarcoma (IFS)DIS-IMT- Inflammatory myofibroblastic tumor (IMT)DIS-SALIVARY- Salivary gland carcinomaDIS-THYROID-ANAPLASTIC- Anaplastic thyroid carcinoma (ATC)DIS-THYROID-PAPILLARY- Papillary thyroid carcinoma (PTC)
Indications
IND-IFS-NTRK-LAROTRECTINIB- IND-IFS-NTRK-LAROTRECTINIBIND-NSCLC-2L-NTRK-LAROTRECTINIB- IND-NSCLC-2L-NTRK-LAROTRECTINIBIND-NSCLC-2L-PD-L1-POST-IO-DOCETAXEL- IND-NSCLC-2L-PD-L1-POST-IO-DOCETAXELIND-NSCLC-DRIVER-NEG-MET-1L-NIVO-IPI-CHEMO- IND-NSCLC-DRIVER-NEG-MET-1L-NIVO-IPI-CHEMOIND-NSCLC-NTRK-FUSION-1L-LAROTRECTINIB- IND-NSCLC-NTRK-FUSION-1L-LAROTRECTINIBIND-PAN-NTRK-2L-REPOTRECTINIB- IND-PAN-NTRK-2L-REPOTRECTINIB
Questionnaires
QUEST-NSCLC-1L-STUB- Non-small cell lung cancer — first line
Red flag
RF-CHOLANGIOCARCINOMA-HIGH-RISK-BIOLOGY- Actionable molecular alteration in cholangiocarcinoma — FGFR2 fusion / rearrangement, IDH...RF-IFS-HIGH-RISK-BIOLOGY- Infantile fibrosarcoma with NTRK fusion identified (ETV6-NTRK3 in >90%, LMNA-NTRK1 / TPM3...RF-IFS-TRANSFORMATION-PROGRESSION- Progression of infantile fibrosarcoma on first-line larotrectinib / entrectinib (acquired...RF-IMT-HIGH-RISK-BIOLOGY- Inflammatory myofibroblastic tumor with actionable fusion driver: ALK fusion (TPM3-ALK, T...RF-SALIVARY-HIGH-RISK-BIOLOGY- Salivary gland carcinoma with actionable molecular driver: ETV6-NTRK3 fusion (mammary ana...RF-THYROID-ANAPLASTIC-HIGH-RISK-BIOLOGY- Anaplastic thyroid carcinoma with actionable driver mutation: BRAF V600E (~25-40% ATC; da...RF-THYROID-PAPILLARY-HIGH-RISK-BIOLOGY- Papillary thyroid carcinoma with adverse molecular / clinical features: BRAF V600E (~60%...