Cemento-osseous dysplasia is caused by RAS-MAPK activation

Cemento-osseous dysplasia (COD) belongs to the spec-trum of benign fibro-osseous lesions occurring exclusively in the tooth-bearing areas of the jaws. Depending on site and extent of involvement, periapical, focal and florid subtypes can be distinguished that share an identical histomorphology. Most cases are asymptomatic and follow a self-limited course requiring no specific treatment. Over time, lesions progressively mineralise while the cellularity decreases. However, the molecular pathogenesis of COD, has not yet been explored. We analysed a series of 31 COD samples by targeted sequencing and detected pathogenic hotspot mutations involving the RAS-MAPK signalling pathway in 5/18 evaluable cases (28%). The mutations were found in the BRAF, HRAS, KRAS, NRAS, and FGFR3 genes. Our findings suggest that COD is driven by RAS-MAPK activation; however, the mechanism underlying the spontaneous growth arrest typically occur-ing in most of the lesions remains elusive.

Automated summary

Cemento-osseous dysplasia (COD) is a benign fibro-osseous lesion that occurs exclusively in the tooth-bearing areas of the jaws. It can be classified into periapical, focal, and florid subtypes based on the site and extent of involvement, which share the same histomorphology. Most cases are asymptomatic and self-limited, requiring no specific treatment. The molecular pathogenesis of COD, specifically the mechanism underlying the spontaneous growth arrest in most lesions, is still unknown.