Novel Gene Fusion Partners in Sarcomas: Focus on NTRK for Targeted Therapy
Posted: Thursday, September 2, 2021
Julie C. Fanburg-Smith, MD, of Milton S. Hershey Medical Center/Penn State College of Medicine, and colleagues aimed to develop a pathologic-radiologic-immunophenotype-genetic/molecular algorithm to aid in the final classification of uncharacterized sarcomas. Published in the Annals of Diagnostic Pathology, their research focused on several cases of various gene fusion partners, including a TPR-NTRK1 fusion and a high-grade KANK1-NTRK2 fusion, with next-generation sequencing paving the way for potentially successful targeted therapy.
The first case involved an 18-year-old male presenting with a 25-cm tumor in the soft tissue and bone of the proximal femur. Initially diagnosed with osteosarcoma, he later underwent a hemipelvectomy due to pathologic fracture. Morphology identified pleomorphic spindled and epithelioid sarcoma, and next-generation sequencing revealed a TPR-NTRK1 fusion. After amputation with completion chemotherapy, the patient is alive with no evidence of disease and approved for future use of the TRK inhibitor larotrectinib.
The second patient was a 41-year-old male presenting with a 10-cm plexiform neurofibroma penetrating bone cortexes in the spine. Pan-TRK immunohistochemistry revealed a KANK1-NTRK2 fusion sarcoma of bone and soft tissue, demonstrating spindled pleomorphic to epithelioid features. The patient still exhibits metastases and will receive larotrectinib upon disease progression.
“NTRK fusions may be found in a wide age range of pediatric and adult soft-tissue tumors and located from superficial to deep, including dermal, subcutaneous, intermuscular, pleural, and dural locations,” the authors commented. “Clinically, recognizing NTRK gene fusions can improve patient outcomes through the use of targeted therapy.”
Disclosure: No disclosure information was provided.