Activating Gsα mutation in intramuscular myxomas with and without fibrous dysplasia of bone

Activating missense mutations in the Arg 201 codon of the gene encoding the α subunit of Gs, the G protein that stimulates cAMP formation, have been recognized as the cause of many endocrine diseases, McCune-Albright syndrome and isolated fibrous dysplasia of bone. On the other hand, intramuscular myxomas with fibrous dysplasia, so-called Mazabraud’s syndrome, have been sporadically reported, but it has not been confirmed whether intramuscular myxoma, with or without fibrous dysplasia, is associated with the Gsα mutations. We investigated the presence of the Gsα mutations in intramuscular myxomas with or without fibrous dysplasia by a PCR-SSCP assay, using formalin-fixed, paraffin-embedded tissues. In five of the six intramuscular myxomas (three with and two without fibrous dysplasia), point mutations were detected as aberrant bands by SSCP, which were confirmed by a subsequent sequence analysis (three Arg to His and two Arg to Cys). This result suggests that the Gsα mutations are related to tumorigenesis in intramuscular myxoma and that intramuscular myxoma is one of the diseases induced by abnormal Gsα protein.