Identification of a novel PRUNE2::NTRK2 gene fusion in soft tissue sarcoma patients-friend or foe? Case series.

Soft tissue sarcomas (STS) are rare mesenchymal tumors in which gene fusions occur in approximately one-third of cases, serving as key diagnostic and therapeutic targets. This study investigates the presence and implications of gene fusions in STS, focusing on a novel PRUNE2::NTRK2 gene fusion identified in two adult patients. The PRUNE2 gene plays a role in cellular processes and is a potential tumor biomarker. PRUNE2 plays a role in various tumors as a tumor suppressor, including prostate cancer, colorectal cancer, and neuroblastoma. The NTRK2 oncogene is, however, associated with tumor progression. In this report, we describe a possible molecular characterization of a novel PRUNE2::NTRK2 gene fusion. Although NTRK-associated fusions are significant in various cancers and have led to the development of targeted therapies, such as larotrectinib and entrectinib, the specific molecular impact of atypical PRUNE2::NTRK2 fusion remains unclear. The PRUNE2::NTRK2 gene fusions described here express a non-functional TrkB protein, and it is unclear whether the PRUNE2 function is intact or affected.