Identification of Trim24 as a new NTRK3 fusion partner in lung adenocarcinoma: Diagnostic challenges of a novel fusion

Reliable neurotrophin kinase (NTRK) fusion assessment is of special relevance since durable responses to targeted therapies have been observed regardless tumor type, NTRK gene or fusion partner. The most prevalent NTRK fusion in solid tumors is the ETV6-NTRK3, although alternative NTRK3 translocations with new partners are increasingly described across a wide variety of tumor types.NTRK fusions occur at low frequencies in non-small-cell lung cancer and are less common than other gene rearrangements. Here we describe a novel TRIM24-NTRK3 fusion in a lung adenocarcinoma patient that was missed by immunohistochemistry and DNA-based NGS but detected using a commercial targeted RNA-based NGS panel. To the best of our knowledge, this fusion has never been previously reported in any cancer type and allowed eligibility of patient for treatment with a small molecule inhibitor. This case also remarks the role of NGS in reliable detection of challenging novel NTRK fusions