{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:41:59Z","timestamp":1780108919588,"version":"3.54.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Paget's disease of bone (PDB) is a focal disorder of bone remodeling that leads to overgrowth of affected bone, with rare progression to osteosarcoma. Extensive studies of familial PDB showed that a majority of cases harbor germline mutations in the Sequestosome1 gene (SQSTM1). In contrast, little is known about the mutational status of SQSTM1 in sporadic PDB. We hypothesized that somatic SQSTM1 mutations might occur in the affected tissues of sporadic PDB and pagetic osteosarcoma. We used laser capture microdissection to capture homogeneous populations of cells from the affected bone or tumor of patients with sporadic PDB or pagetic osteosarcoma, respectively. DNA from these samples and appropriate controls was used for sequence analysis and allelic discrimination analysis. Two of five patients with sporadic PDB had SQSTM1C1215T mutations detected in their affected bone but not in their blood samples, indicating a somatic origin of the mutations. Samples from three of five sporadic pagetic osteosarcoma patients had the SQSTM1C1215T mutation, whereas the normal adjacent tissue from two of these tumors clearly lacked the mutation, again indicating an occurrence of somatic events. No SQSTM1 mutations were found in primary adolescent osteosarcomas. The discovery of somatic SQSTM1 mutations in sporadic PDB and pagetic osteosarcoma shows a role for SQSTM1 in both sporadic and inherited PDB. The discovery of somatically acquired mutations in both the diseased bone and tumor samples suggests a paradigm shift in our understanding of this disease.<\/jats:p>","DOI":"10.1359\/jbmr.081105","type":"journal-article","created":{"date-parts":[[2008,11,18]],"date-time":"2008-11-18T14:32:29Z","timestamp":1227018749000},"page":"484-494","source":"Crossref","is-referenced-by-count":54,"title":["Somatic Mutations in <i>SQSTM1<\/i> Detected in Affected Tissues From Patients With Sporadic Paget's Disease of Bone"],"prefix":"10.1093","volume":"24","author":[{"given":"Anand","family":"Merchant","sequence":"first","affiliation":[{"name":"Present address: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA"},{"name":"Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"Smielewska","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Connecticut Health Center, Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimit","family":"Patel","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer D","family":"Akunowicz","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A","family":"Saria","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D","family":"Delaney","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Connecticut Health Center, Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J","family":"Leach","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Seton","sequence":"additional","affiliation":[{"name":"New England Registry for Paget's Disease of Bone, Massachusetts General Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc F","family":"Hansen","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024020320041701300_bib1","first-page":"320","volume-title":"Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism","author":"Siris","year":"2006","edition":"6th ed"},{"key":"2024020320041701300_bib2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1097\/00002281-199707000-00013","article-title":"Paget's disease of bone","volume":"9","author":"Fraser","year":"1997","journal-title":"Curr Opin Rheumatol"},{"key":"2024020320041701300_bib3","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1359\/jbmr.1998.13.7.1061","article-title":"Paget's disease of bone","volume":"13","author":"Siris","year":"1998","journal-title":"J Bone Miner Res"},{"key":"2024020320041701300_bib4","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/00000478-197902000-00006","article-title":"Premalignant tumors and conditions of bone","volume":"3","author":"Unni","year":"1979","journal-title":"Am J Surg Pathol"},{"key":"2024020320041701300_bib5","first-page":"126","author":"Maldague","year":"1987"},{"key":"2024020320041701300_bib6","first-page":"496","article-title":"Sarcoma complicating Paget's disease of bone. 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