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

Activating missense mutations in the Arg 201 codon of the gene encoding the alpha subunit of Gs, the G protein that stimulates cAMP formation, have be en recognized as the cause of many endocrine diseases, McCune-Albright synd rome and isolated fibrous dysplasia of bone. On the other hand, intramuscul ar myxomas with fibrous dysplasia, so-called Mazabraud's syndrome, have bee n sporadically reported, but it has not been confirmed whether intramuscula r myxoma, with or without fibrous dysplasia, is associated with the Gs alph a mutations. We investigated the presence of the Cs alpha mutations in intr amuscular myxomas with or without fibrous dysplasia by a PCR-SSCP assay, us ing formalin-fixed, paraffin-embedded tissues. In five of the six intramusc ular myxomas (three with and two without fibrous dysplasia), point mutation s were detected as aberrant bands by SSCP, which were confirmed by a subseq uent sequence analysis (three Arg to His and two Arg to Cys). This result s uggests that the Gs alpha mutations are related to tumorigenesis in intramu scular myxoma and that intramuscular myxoma is one of the diseases induced by abnormal Gs alpha protein.