Molecular Markers of Fibro-Osseous Lesions and Osteosarcomas of the Craniofacial Complex—Current Situation and Recent Advances

Fibro-osseous lesions share clinical, radiological, and pathological features, particularly in the craniofacial complex, a location where diagnosing these lesions is challenging. Some molecular markers involved in the pathogenesis of these lesions offer significant diagnostic support. Guanine nucleotide-binding protein/alpha subunit (GNAS) mutations are specific to fibrous dysplasias and are not encountered in ossifying fibromas (including juvenile variants), or in low-grade and high-grade osteosarcomas of the jaw. Low-grade and dedifferentiated osteosarcomas show murine double-minute 2 (MDM2) amplification, with overexpression of MDM2, abnormalities not encountered in fibrous dysplasia, or in ossifying fibroma. No recurrent cytogenetic or molecular abnormality has been reported to date in conventional ossifying fibromas. The juvenile variants of ossifying fibroma exhibit MDM2/RAS protein activator like-1 (RASAL1) co-amplification, without MDM2 overexpression, abnormalities also observed in certain aggressive osteosarcomas of the jaw, which may derive from juvenile ossifying fibroma. MDM2/RASAL1 co-amplification may constitute an early molecular marker of aggressive juvenile ossifying fibroma and may indicate a need for closer follow-up and more radical treatment.