GNAS mutations are not detected in parosteal and low-grade central osteosarcomas

Author(s):Show less -

Salinas-Souza, Carolina ^{[1, 2]} ; De Andrea, Carlos ^{[3, 1]} ; Bihl, Michel ^[4] ; Kovac, Michal ^[5] ; Pillay, Nischalan ^{[3, 6]} ; Forshew, Tim ^[6] ; Gutteridge, Alice ^[6] ; Ye, Hongtao ^[3] ; Amary, M. Fernanda ^{[3, 6]} ; Tirabosco, Roberto ^[3] ; Toledo, Silvia Regina Caminada ^[2] ; Baumhoer, Daniel ^[5] ; Flanagan, Adrienne M. ^{[3, 6]}

Affiliation

^[1] UCL, Inst Canc, Sarah Cannon UCL Labs, UCL Adv Diagnost Mol Profiling Lab, London WC1E 6BT - England

^[2] Univ Sao Paulo, Pediat Oncol Inst, Sao Paulo - Brazil

^[3] Royal Natl Orthopaed Hosp NHS Trust, Stanmore, Middx - England

^[4] Univ Basel Hosp, Inst Pathol, CH-4031 Basel - Switzerland

^[5] Univ Basel Hosp, Bone Tumour Reference Ctr, CH-4031 Basel - Switzerland

^[6] UCL, Inst Canc, London WC1E 6BT - England

• Document type: Journal article
• Source: MODERN PATHOLOGY; v. 28, n. 10, p. 1336-1342, OCT 2015.
• Web of Science Citations: 16

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. (AU)

• FAPESP's process: 13/13573-9 - Determining the clinical impact of genetic alterations in osteosarcoma
• Grantee: Carolina Salinas de Souza
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor