Activating mutations of Gs protein in monostotic fibrous lesions of bone.
Activating mutations of the alpha chain of the heterotrimeric signal transducer Gs disrupt the inherent guanosine triphosphatase activity of the alpha chain, stimulate adenylyl cyclase, and can result in independent cell proliferation. Such mutations are identified in a number of endocrine disorders, including McCune-Albright syndrome, which is a triad of endocrinopathy, café au lait spots, and polyostotic fibrous dysplasia. The mutation in this syndrome is a missense point mutation in exon 8 that results in the substitution of either histidine or cysteine for arginine at position 201. Monostotic fibrous dysplasia is a nonhereditary isolated bone lesion. Other isolated bone lesions that share some cytologic and clinical similarities to fibrous dysplasia are osteofibrous dysplasia and aggressive fibromatosis involving bone. Four cases of monostotic fibrous dysplasia, four cases of aggressive fibromatosis involving bone, and one case of osteofibrous dysplasia were studied to determine if a mutation was present in exon 8 of the alpha chain of Gs. A missense mutation was present in all of the fibrous dysplasias. The other fibrous lesions and uninvolved tissue did not contain a mutation. Somatic activating mutations of Gs differentiate fibrous dysplasia from the other lesions and may be responsible for the loss of control of local proliferation and growth factor expression.
Alman
B A
BA
Department of Orthopaedics, New England Medical Center Hospitals, Boston, Massachusetts, USA.
Greel
D A
DA
Wolfe
H J
HJ
D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D018222:Desmoid Tumors / Q000235:genetics / Q000473:pathology; D005357:Fibrous Dysplasia of Bone / Q000235:genetics / Q000473:pathology; D005358:Fibrous Dysplasia, Monostotic / Q000235:genetics* / Q000473:pathology; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation
D019204:GTP-Binding Proteins