FOS gene fusions in osteosarcoma raise the hypothesis of malignant transformation of osteoblastoma.
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
Osteosarcoma is the most common malignant bone tumor among children and young adults. Distinguishing between osteoblastoma and osteosarcoma can be particularly challenging, especially in small tissue samples and for the osteoblastoma-like osteosarcoma subtype. Recent studies with conflicting results have suggested a potential malignant transformation process from osteoblastoma to osteosarcoma. This study aims to investigate the hypothesis of osteoblastoma evolving into osteosarcoma and to discuss its clinical implications. We conducted a retrospective multicentric case-series study, collecting clinical, radiological, histological, and follow-up data from osteosarcoma cases suspected to have originated from malignant transformation of osteoblastoma within the French ResOs network. Molecular analyses (fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS)) were performed. We included two cases (one female and one male), with a median age at osteosarcoma diagnosis of 42 and 73 years old, respectively. One patient had tumor located in the axial skeleton, and both cases exhibited features of osteoblastoma-like osteosarcoma. Notably, one of the patients had a documented history of osteoblastoma diagnosed sixteen years earlier. FISH analysis revealed FOS rearrangements in both osteosarcoma cases, with tumors presenting uncommon fusion transcripts (FOS::VGLL4 and FOS::COL5A2) identified through NGS. Both patients were alive at last follow-up. Our findings suggest that osteosarcoma can rarely present with FOS gene fusions and be associated with an indolent progression, challenging the specificity of such signatures for osteoblastoma diagnosis. This discovery also raises the hypothesis of malignant transformation from osteoblastoma to osteosarcoma and underscores the necessity for diligent monitoring of FOS-rearranged bone-forming tumors for optimal therapeutic management.