A pan-cancer analysis identified 358 distinct NTRK fusion-tumor pairings across 25 tumor types after testing the literature, clinical trial, and genomic databases — including 229 different fusion partners overall. In the study, primary CNS tumors harbored 86 distinct NTRK fusions and sarcomas 73, underscoring how broadly these actionable alterations can vary across malignant neoplasm types.

Why It Matters To Your Practice

• NTRK fusions are established oncogenic drivers in adult and pediatric cancers and can make patients eligible for FDA-approved TRK inhibitors.

• The breadth of fusion partners means a negative or incomplete single-target approach may miss clinically relevant rearrangements.

• ETV6 :: NTRK3 appeared across the greatest number of tumor types, but most partners were far rarer and more tumor-specific.

Clinical Benefits

• Broad, fusion-partner agnostic testing can help identify both known and novel NTRK rearrangements across diverse cancers.

• Finding an actionable NTRK fusion may open the door to tumor-agnostic targeted therapy rather than relying only on histology-based treatment choices.

• This is especially relevant in CNS tumors and sarcomas, where the analysis found the highest numbers of distinct fusions.

Managing Risks

• Do not assume a common partner is the only clinically relevant one: 183 fusion partners were linked to just a single NTRK gene in one tumor type.

• When ordering molecular testing, favor assays designed to detect rearrangements broadly rather than only a short list of expected partners.

• Interpret results in clinical context and coordinate with oncology, pathology, and molecular diagnostics teams when novel fusions are reported.

The Bottom Line

• NTRK fusions are highly heterogeneous across cancers, with 229 distinct partners identified in this descriptive compendium.

• For NPs and PAs, the practical takeaway is to think broadly about molecular testing strategy so eligible patients are not missed for TRK inhibitor therapy.