{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T07:45:02Z","timestamp":1770450302959,"version":"3.49.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,6]],"date-time":"2017-06-06T00:00:00Z","timestamp":1496707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,6]],"date-time":"2017-06-06T00:00:00Z","timestamp":1496707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Guanine nucleotide-binding protein\/\u03b1-subunit (<jats:italic>GNAS<\/jats:italic>) mutations are involved in fibrous dysplasia (FD) pathogenesis. Here, we analyzed <jats:italic>GNAS<\/jats:italic> mutations in FD which were performed by pyrosequencing DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue. The mutation detection rate was determined in FD specimens with and without decalcification. <jats:italic>GNAS<\/jats:italic> mutation was identified in 28 cases out of 87 FDs (32.18%) [p.R201C (<jats:italic>N<\/jats:italic>\u2009=\u200914) and p.R201H (<jats:italic>N<\/jats:italic>\u2009=\u200914)]. <jats:italic>GNAS<\/jats:italic> mutation was more likely to occur in polyostotic FD (7\/28, 25.0%); FD without <jats:italic>GNAS<\/jats:italic> mutation was mostly monostotic form (56\/59, 94.9%, <jats:italic>P<\/jats:italic>\u2009=\u20090.011). The G\u2009&gt;\u2009A (R201H) mutation was more frequent in polyostotic FD (6\/14 patients, 42.9%) than the C\u2009&gt;\u2009T (R201C) mutation (1\/14, 7.1%) (<jats:italic>P<\/jats:italic>\u2009=\u20090.077). We divided the FD cases into two subgroups: tissue specimens that were not decalcified (<jats:italic>N<\/jats:italic>\u2009=\u200935, 40.2%), and tissue specimens that were decalcified (<jats:italic>N<\/jats:italic>\u2009=\u200952, 59.8%). <jats:italic>GNAS<\/jats:italic> mutation was more frequently identified in FD specimens that were not subjected to decalcification (23\/35, 65.7%) than in FD specimens that were decalcified (5\/52, 9.6%) (<jats:italic>P<\/jats:italic>\u2009=\u20090.001). In conclusion, mutation analysis of <jats:italic>GNAS<\/jats:italic> by pyrosequencing has diagnostic value in FFPE tissue of patients with FD, especially in specimens that were not decalcified. The R201H substitution mutation of <jats:italic>GNAS<\/jats:italic> may be involved in the pathogenesis of polyostotic FD.<\/jats:p>","DOI":"10.1038\/s41598-017-03093-1","type":"journal-article","created":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T09:24:40Z","timestamp":1496222680000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Frequency of GNAS R201H substitution mutation in polyostotic fibrous dysplasia: Pyrosequencing analysis in tissue samples with or without decalcification"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9114-8438","authenticated-orcid":false,"given":"Su-Jin","family":"Shin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seok Joo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Kyum","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,6,6]]},"reference":[{"key":"3093_CR1","first-page":"179","volume":"57","author":"LW Gorham","year":"1941","unstructured":"Gorham, L. 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Ann Pathol \n                           21, 489\u2013498 (2001).","journal-title":"Ann Pathol"},{"key":"3093_CR4","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1038\/modpathol.2009.32","volume":"22","author":"D Delaney","year":"2009","unstructured":"Delaney, D. et al. GNAS1 mutations occur more commonly than previously thought in intramuscular myxoma. Mod Pathol \n                           22, 718\u2013724, doi:10.1038\/modpathol.2009.32 (2009).","journal-title":"Mod Pathol"},{"key":"3093_CR5","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1056\/NEJM199112123252403","volume":"325","author":"LS Weinstein","year":"1991","unstructured":"Weinstein, L. S. et al. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med \n                           325, 1688\u20131695, doi:10.1056\/NEJM199112123252403 (1991).","journal-title":"N Engl J Med"},{"key":"3093_CR6","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1210\/jcem.79.3.8077356","volume":"79","author":"A Shenker","year":"1994","unstructured":"Shenker, A., Weinstein, L. S., Sweet, D. E. & Spiegel, A. M. An activating Gs alpha mutation is present in fibrous dysplasia of bone in the McCune-Albright syndrome. J Clin Endocrinol Metab \n                           79, 750\u2013755, doi:10.1210\/jcem.79.3.8077356 (1994).","journal-title":"J Clin Endocrinol Metab"},{"key":"3093_CR7","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1359\/jbmr.2000.15.1.120","volume":"15","author":"P Bianco","year":"2000","unstructured":"Bianco, P. et al. Mutations of the GNAS1 gene, stromal cell dysfunction, and osteomalacic changes in non-McCune-Albright fibrous dysplasia of bone. J Bone Miner Res \n                           15, 120\u2013128, doi:10.1359\/jbmr.2000.15.1.120 (2000).","journal-title":"J Bone Miner Res"},{"key":"3093_CR8","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1002\/jor.1100140221","volume":"14","author":"BA Alman","year":"1996","unstructured":"Alman, B. A., Greel, D. A. & Wolfe, H. J. Activating mutations of Gs protein in monostotic fibrous lesions of bone. J Orthop Res \n                           14, 311\u2013315, doi:10.1002\/jor.1100140221 (1996).","journal-title":"J Orthop Res"},{"key":"3093_CR9","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/S8756-3282(97)00107-5","volume":"21","author":"GA Candeliere","year":"1997","unstructured":"Candeliere, G. A., Roughley, P. J. & Glorieux, F. H. Polymerase chain reaction-based technique for the selective enrichment and analysis of mosaic arg201 mutations in G alpha s from patients with fibrous dysplasia of bone. 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J Bone Joint Surg Am \n                           87, 2489\u20132494, doi:10.2106\/JBJS.E.00160 (2005).","journal-title":"J Bone Joint Surg Am"},{"key":"3093_CR12","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1359\/jbmr.1999.14.11.1987","volume":"14","author":"M Riminucci","year":"1999","unstructured":"Riminucci, M. et al. A novel GNAS1 mutation, R201G, in McCune-albright syndrome. J Bone Miner Res \n                           14, 1987\u20131989, doi:10.1359\/jbmr.1999.14.11.1987 (1999).","journal-title":"J Bone Miner Res"},{"key":"3093_CR13","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1111\/j.1365-2559.2007.02676.x","volume":"50","author":"BD Idowu","year":"2007","unstructured":"Idowu, B. D. et al. A sensitive mutation-specific screening technique for GNAS1 mutations in cases of fibrous dysplasia: the first report of a codon 227 mutation in bone. Histopathology \n                           50, 691\u2013704, doi:10.1111\/j.1365-2559.2007.02676.x (2007).","journal-title":"Histopathology"},{"key":"3093_CR14","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1016\/j.humpath.2011.09.012","volume":"43","author":"SE Lee","year":"2012","unstructured":"Lee, S. E. et al. The diagnostic utility of the GNAS mutation in patients with fibrous dysplasia: meta-analysis of 168 sporadic cases. Hum Pathol \n                           43, 1234\u20131242, doi:10.1016\/j.humpath.2011.09.012 (2012).","journal-title":"Hum Pathol"},{"key":"3093_CR15","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1038\/modpathol.2012.223","volume":"26","author":"F Tabareau-Delalande","year":"2013","unstructured":"Tabareau-Delalande, F. et al. Diagnostic value of investigating GNAS mutations in fibro-osseous lesions: a retrospective study of 91 cases of fibrous dysplasia and 40 other fibro-osseous lesions. Mod Pathol \n                           26, 911\u2013921, doi:10.1038\/modpathol.2012.223 (2013).","journal-title":"Mod Pathol"},{"key":"3093_CR16","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1038\/modpathol.2013.31","volume":"26","author":"RR Shi","year":"2013","unstructured":"Shi, R. R., Li, X. F., Zhang, R., Chen, Y. & Li, T. J. GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw. Mod Pathol \n                           26, 1023\u20131031, doi:10.1038\/modpathol.2013.31 (2013).","journal-title":"Mod Pathol"},{"key":"3093_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.prp.2013.09.003","volume":"210","author":"I Walther","year":"2014","unstructured":"Walther, I., Walther, B. M., Chen, Y. & Petersen, I. Analysis of GNAS1 mutations in myxoid soft tissue and bone tumors. 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J Mol Diagn \n                           13, 137\u2013142, doi:10.1016\/j.jmoldx.2010.10.003 (2011).","journal-title":"J Mol Diagn"},{"key":"3093_CR20","doi-asserted-by":"publisher","first-page":"5152","DOI":"10.1073\/pnas.89.11.5152","volume":"89","author":"WF Schwindinger","year":"1992","unstructured":"Schwindinger, W. F., Francomano, C. A. & Levine, M. A. Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome. Proc Natl Acad Sci USA \n                           89, 5152\u20135156, doi:10.1073\/pnas.89.11.5152 (1992).","journal-title":"Proc Natl Acad Sci USA"},{"key":"3093_CR21","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1136\/mp.53.6.336","volume":"53","author":"CL Wickham","year":"2000","unstructured":"Wickham, C. L. et al. Formic acid decalcification of bone marrow trephines degrades DNA: alternative use of EDTA allows the amplification and sequencing of relatively long PCR products. Mol Pathol \n                           53, 336\u2013336, doi:10.1136\/mp.53.6.336 (2000).","journal-title":"Mol Pathol"},{"key":"3093_CR22","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1097\/00005792-199607000-00001","volume":"75","author":"MD Ringel","year":"1996","unstructured":"Ringel, M. D., Schwindinger, W. F. & Levine, M. A. Clinical implications of genetic defects in G proteins. The molecular basis of McCune-Albright syndrome and Albright hereditary osteodystrophy. Medicine (Baltimore) \n                           75, 171\u2013184, doi:10.1097\/00005792-199607000-00001 (1996).","journal-title":"Medicine (Baltimore)"},{"key":"3093_CR23","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1023\/A:1005393501786","volume":"20","author":"AM Spiegel","year":"1997","unstructured":"Spiegel, A. M. Inborn errors of signal transduction: mutations in G proteins and G protein-coupled receptors as a cause of disease. J Inherit Metab Dis \n                           20, 113\u2013121, doi:10.1023\/A:1005393501786 (1997).","journal-title":"J Inherit Metab Dis"},{"key":"3093_CR24","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1159\/000185441","volume":"47","author":"AM Spiegel","year":"1997","unstructured":"Spiegel, A. M. The molecular basis of disorders caused by defects in G proteins. Horm Res \n                           47, 89\u201396, doi:10.1159\/000185441 (1997).","journal-title":"Horm Res"},{"key":"3093_CR25","first-page":"1059","volume":"150","author":"PJ Marie","year":"1997","unstructured":"Marie, P. J., de Pollak, C., Chanson, P. & Lomri, A. Increased proliferation of osteoblastic cells expressing the activating Gs alpha mutation in monostotic and polyostotic fibrous dysplasia. 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A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to Gsalpha mutation at the Arg201 codon: polymerase chain reaction-restriction fragment length polymorphism analysis of paraffin-embedded tissues. J Mol Diagn \n                           2, 67\u201372, doi:10.1016\/S1525-1578(10)60618-6 (2000).","journal-title":"J Mol Diagn"},{"key":"3093_CR28","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/modpathol.3800753","volume":"20","author":"S Toyosawa","year":"2007","unstructured":"Toyosawa, S. et al. Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization. Mod Pathol \n                           20, 389\u2013396, doi:10.1038\/modpathol.3800753 (2007).","journal-title":"Mod Pathol"},{"key":"3093_CR29","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/S0901-5027(99)80085-X","volume":"28","author":"MM Cohen Jr.","year":"1999","unstructured":"Cohen, M. M. Jr. & Howell, R. E. Etiology of fibrous dysplasia and McCune-Albright syndrome. Int J Oral Maxillofac Surg \n                           28, 366\u2013371, doi:10.1016\/S0901-5027(99)80085-X (1999).","journal-title":"Int J Oral Maxillofac Surg"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03093-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03093-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03093-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T04:55:48Z","timestamp":1671771348000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03093-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,6]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["3093"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-03093-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,6]]},"assertion":[{"value":"2 February 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"2836"}}