<i>NTRK</i> Gene Fusions: A Compendium of Fusion Partners and Tumor Types.

Abstract

<i>NTRK</i> gene fusions are oncogenic drivers for a variety of adult and pediatric tumors, making them a target for tumor-agnostic precision medicine. Tropomyosin receptor kinase (TRK) inhibitors are approved by the US Food and Drug Administration for cancers driven by TRK fusions. However, <i>NTRK</i> genes can fuse with many different partner genes, leading to diverse TRK fusion proteins, highlighting the importance of identifying the specific fusion partner with optimal pan-cancer diagnostics. This analysis aims to provide an updated descriptive compendium of <i>NTRK</i> gene fusions. <i>NTRK</i> gene fusions were identified via literature searches (PubMed), a search of a clinical trials database (larotrectinib), and searches of two genomic databases (Memorial Sloan Kettering and Children's Hospital of Philadelphia). In total, 358 distinct <i>NTRK</i> gene fusion-tumor pairings were identified across 25 tumor types. Primary CNS tumors were observed to harbor 86 distinct <i>NTRK</i> gene fusions, followed by sarcomas (n = 73). Overall, 229 different fusion partners were identified across tumor types (regardless of <i>NTRK</i> gene). Twenty-three fusion partners were found to fuse with >1 <i>NTRK</i> gene across tumor types, while 183 fusion partners were associated with only a single <i>NTRK</i> gene in one tumor type. <i>ETV6</i>::<i>NTRK3</i> was found in the highest number of different tumor types. This analysis illustrates the diversity of <i>NTRK</i> gene fusion partners across various tumor types and highlights the importance of selecting a pan-tumor fusion-partner agnostic test that can identify both known and novel fusion partners to identify patients who may benefit from treatment with TRK inhibitors.