A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to G_Sα mutation at the Arg²⁰¹ codon: Polymerase chain reaction-restriction fragment length polymorphism analysis of paraffin-embedded tissues

Fibrous dysplasia and osteofibrous dysplasia are both benign fibro-osseous lesions of the bone and are generally seen during childhood or adolescence. Histologically, the features of these bone lesions sometimes look quite similar, but their precise nature remains controversial. Mutation of the α subunit of signal-transducing G proteins (G_Sα), with an increase in cyclic adenosine monophosphate (cAMP) formation, has been implicated in the development of multiple endocrinopathies of the Albright-McCune syndrome and in the development of fibrous dysplasia. We studied G_Sα mutation at the Arg²⁰¹ codon in seven cases of fibrous dysplasia (six monostotic lesions and one polyostotic lesion) and seven cases of osteofibrous dysplasia using formalin-fixed, paraffin-embedded tissue, by means of polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. All of the seven cases of fibrous dysplasia showed missense point mutations in G_Sα at the Arg²⁰¹ codon that resulted in Arg-to-His substitution in three cases and Arg-to-Cys substitution in four cases. On the other hand, the seven cases of osteofibrous dysplasia and the normal bone used as a control showed no such mutation. These data suggest that fibrous dysplasia and osteofibrous dysplasia have different pathogeneses and that the detection of G_Sα mutation at the Arg²⁰¹ codon is quite useful for distinguishing between these lesions.