NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)

These findings highlight the value of RNA-based NGS, particularly when used alongside DNA NGS, to provide a comprehensive assessment of NTRK fusions and co-occurring gene alterations. Implementation of combined DNA and RNA CGP in a community health system setting enables detection of both known and novel NTRK fusions and can inform clinical care of cancer patients.

P2, N=73, Active, not recruiting, BicycleTx Limited | Recruiting --> Active, not recruiting

A novel in-frame gene fusion (TMEM79::NTRK1) was identified in a single tumor sample (0.5%). Our results confirm that LCNECs harbor potentially targetable alterations in KRAS, PIK3CA, RET, BRAF, and NTRK1, albeit at lower frequencies than those typically observed in NSCLC.

Functional NTRK fusion-positive tumors comprise biologically and clinically distinct subsets defined by tumor type and MSI/TMB context. Concurrent reporting of MSI/TMB (and HRD/EBV when available) together with NTRK fusion status may facilitate integrated clinical interpretation, support precision treatment selection, and refine trial stratification in clinical practice.

These findings demonstrate that IHC-based screening followed by confirmatory FISH provides a rapid and cost-effective strategy for identifying cases of non-LCH with JXG morphology harboring actionable kinase alterations. Integration of IHC, FISH, and NGS represents a practical and complementary diagnostic strategy to guide precision therapy in this clinically diverse histiocytic disorder.

These findings establish LGMS as a genomically stable, epigenetically distinct myofibroblastic sarcoma driven by USP6 overexpression and an inflammation-enriched transcriptome. They support its recognition as a standalone entity, facilitate integration into methylation-based sarcoma classifiers for improved diagnostic precision, and nominate USP6-associated pathways and immune checkpoint blockade as promising therapeutic strategies for recurrent or unresectable disease.

We define a novel gut-thyroid axis where Terrisporobacter contributes to PTC development by upregulating the NTRK1 oncogene and shaping a pro-tumorigenic, immunosuppressive microenvironment. These findings reveal a new dimension of host-microbe interaction in thyroid cancer and highlight the TME as a key downstream target of microbial influence.

P2, N=32, Completed, The University of Sydney | Active, not recruiting --> Completed

This study highlights the importance of targeted NGS combined with FISH and clinicopathological analysis for accurate diagnosis in NTRK fusion PTC. While pan-TRK IHC is useful for initial screening, confirmatory NGS is essential to avoid false-negative results.

Owing to the presence of neural tissue, NTRKs are highly positive in IHC, making these genes unsuitable as biomarkers for assessing NTRK inhibitor sensitivity and resistance, which are tissue-agnostic drugs. The observed low fusion rate is consistent with the literature, and the significance of the numerous point mutations identified as agnostic markers warrants further investigation. NTRK expression, fusion, and point mutations were not associated with clinical parameters or survival.

This case highlights the power of comprehensive molecular profiling and high-frequency ctDNA monitoring to capture tumor evolution and minimal residual disease. Importantly, it further demonstrates how MRD-guided surveillance enables a precise balance between fast-acting targeted therapy and the sustained effects of immunotherapy, providing a blueprint for individualized, context- driven treatment strategies in rare molecular subtypes of pancreatic cancer.

P1/2, N=28, Active, not recruiting, Bicycletx Limited | Recruiting --> Active, not recruiting