title: GNAS mutations are not detected in parosteal and low-grade central osteosarcomas.
abstract: Parosteal osteosarcoma, low-grade central osteosarcoma, and fibrous dysplasia share similar histological features that may pose a diagnostic challenge. The detection of GNAS mutations in primary bone tumors has been useful in clinical practice for diagnosing fibrous dysplasia. However, the recent report of GNAS mutations being detected in a significant proportion of parosteal osteosarcoma challenges the specificity of this mutation. As the number of cases reported in this study was small we set out to determine if these results could be reproduced. We studied 97 formalin-fixed paraffin-embedded low-grade osteosarcomas from 90 patients including 62 parosteal osteosarcomas, of which MDM2 amplification was detected in 79%, 11 periosteal osteosarcomas and 24 low-grade central osteosarcoma samples. The mutational status of GNAS was analyzed in codons p.R201, p.Q227, and other less common GNAS alterations by bidirectional Sanger sequencing and/or next generation sequencing using the Life Technologies Ion Torrent platform. GNAS mutations were not detected in any of the low-grade osteosarcomas from which informative DNA was extracted. Our findings therefore support prior observations that GNAS mutations are highly specific for fibrous dysplasia and occur rarely, if ever, in parosteal and other low-grade osteosarcomas.
authors.affiliation: UCL Advanced Diagnostics Molecular Profiling Laboratory, Sarah Cannon-UCL Laboratories, UCL Cancer Institute, London, UK.|Pediatric Oncology Institute/Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Salinas-Souza
authors.affiliation: UCL Advanced Diagnostics Molecular Profiling Laboratory, Sarah Cannon-UCL Laboratories, UCL Cancer Institute, London, UK.|Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, UK.
authors.forename: Carlos
authors.initials: C
authors.lastname: De Andrea
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Bihl
authors.affiliation: Bone Tumour Reference Centre, University Hospital Basel, Basel, Switzerland.
authors.forename: Michal
authors.initials: M
authors.lastname: Kovac
authors.affiliation: Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, UK.|UCL Cancer Institute, London, UK.
authors.forename: Nischalan
authors.initials: N
authors.lastname: Pillay
authors.affiliation: UCL Cancer Institute, London, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Forshew
authors.affiliation: UCL Cancer Institute, London, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Gutteridge
authors.affiliation: Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, UK.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ye
authors.affiliation: Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, UK.|UCL Cancer Institute, London, UK.
authors.forename: M Fernanda
authors.identifier: http://orcid.org/0000-0002-6707-8246
authors.initials: MF
authors.lastname: Amary
authors.affiliation: Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, UK.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tirabosco
authors.affiliation: Pediatric Oncology Institute/Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Silvia Regina Caminada
authors.initials: SR
authors.lastname: Toledo
authors.affiliation: Bone Tumour Reference Centre, University Hospital Basel, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Baumhoer
authors.affiliation: Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, UK.|UCL Cancer Institute, London, UK.
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Flanagan
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology*; D002864:Chromogranins; D004252:DNA Mutational Analysis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005784:Gene Amplification; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics
chemical_list: D002864:Chromogranins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs