title: Activating GNAS mutations in parosteal osteosarcoma.
abstract: Parosteal osteosarcoma is a surface-based osteosarcoma that often exhibits deceptively bland cytologic features, hindering diagnosis in small biopsies or when correlative radiologic imaging is not readily available. A number of benign and malignant fibro-osseous lesions, including fibrous dysplasia (FD) and low-grade central osteosarcoma, fall within the morphologic differential diagnosis of parosteal osteosarcoma. Somatic mutations in GNAS, encoding the α-subunit of the heterotrimeric G protein complex (Gsα), occur in FD and McCune-Albright syndrome but have not been reported in parosteal osteosarcoma. We evaluated GNAS mutational status in parosteal osteosarcoma and several of its histologic mimics to determine its utility in differentiating these entities. Eleven of 14 (79%) FD cases had GNAS mutations within codon 201 (5 R201C and 6 R201H mutations). GNAS mutations were not detected in any cases of adamantinoma or osteofibrous dysplasia. Direct sequencing of 9 parosteal osteosarcomas, including 3 of low grade and 6 with dedifferentiation, revealed activating GNAS mutations in 5 cases (55%), distributed as 4 R201C-mutated tumors and 1 tumor with an R201H mutation. GNAS codon 227 mutations were not detected in any of the cases. There was no association between GNAS mutational status and patient demographics, histologic dedifferentiation, or clinical outcome. To our knowledge, we report the first series of parosteal osteosarcomas harboring activating GNAS mutations. Our data suggest that GNAS mutational status may have limited utility as an ancillary technique in differentiating benign and malignant fibro-osseous lesions of the bone.
authors: Departments of *Laboratory Medicine and Pathology †Radiology, Mayo Clinic, Rochester, MN.
authors: Jodi M
authors: JM
authors: Carter
authors: Carrie Y
authors: CY
authors: Inwards
authors: Long
authors: L
authors: Jin
authors: Barbara
authors: B
authors: Evers
authors: Doris E
authors: DE
authors: Wenger
authors: Andre M
authors: AM
authors: Oliveira
authors: Karen J
authors: KJ
authors: Fritchie
mesh_terms: D050398:Adamantinoma / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001848:Bone Diseases, Developmental / Q000235:genetics / Q000473:pathology; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D054337:Cell Dedifferentiation; D002648:Child; D002864:Chromogranins; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005357:Fibrous Dysplasia of Bone / Q000235:genetics / Q000473:pathology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D012516:Osteosarcoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs