title: Quantitative analysis of activating alpha subunit of the G protein (Gsα) mutation by pyrosequencing in fibrous dysplasia and other bone lesions.
abstract: Benign fibro-osseous lesions (BFOLs) frequently display overlapping histological features. The differentiation of fibrous dysplasia (FD) from other BFOLs can be difficult, even for experienced orthopedic pathologists. Accurately distinguishing FD from other BFOLs may have significant clinical and treatment implications. A somatic mutation in gene GNAS encoding the α subunit of the G protein (Gsα) involving the codon corresponding to Arg 201 has been identified in FD and is specifically absent in other BFOLs. We have developed a quantitative assay by pyrosequencing that has a detection sensitivity of 95%. The test allows the identification of the two most common types of mutation (Arg→His and Arg→Cys) in a single reaction, with the ability to analyze other rare mutations. Of the 24 FD cases in this series, 23 (96%) were positive for GNAS/Gsα mutation. Nineteen of 23 positive cases exhibited a G→A mutation (Arg→His), whereas four had a C→T mutation (Arg→Cys). One of three BFOL, not otherwise specified cases was positive for G→A mutation. None of the osteofibrous dysplasia, ossifying fibromas, or other bone lesions were positive for this mutation. Our experience is that pyrosequencing is an easy and accurate quantification method for Gsα mutation detection in fibrous dysplasia. Mutation analysis of the Gsα by pyrosequencing has significant potential for improving discrimination between FD and other BFOLs in problematic cases.
authors.affiliation: Division of Molecular Pathology, Department of Scientific Laboratories, Armed Forces Institute of Pathology, Washington, DC 20306, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liang
authors.forename: Minqi
authors.initials: M
authors.lastname: Wei
authors.forename: LeAnn
authors.initials: L
authors.lastname: Hodge
authors.forename: Julie C
authors.initials: JC
authors.lastname: Fanburg-Smith
authors.forename: Ann
authors.initials: A
authors.lastname: Nelson
authors.forename: Markku
authors.initials: M
authors.lastname: Miettinen
authors.forename: Robert D
authors.initials: RD
authors.lastname: Foss
authors.forename: Guanghua
authors.initials: G
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001847:Bone Diseases / Q000235:genetics* / Q000473:pathology; D001848:Bone Diseases, Developmental / Q000235:genetics* / Q000473:pathology; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D019205:GTP-Binding Protein alpha Subunits, Gs