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dc.contributor.authorAli, Naser M
dc.contributor.authorNiada, Stefania
dc.contributor.authorMorris, Mark R
dc.contributor.authorBrini, Anna T
dc.contributor.authorHuen, David
dc.contributor.authorSumathi, Vaiyapuri
dc.contributor.authorLatif, Farida
dc.date.accessioned2019-05-31T11:04:17Z
dc.date.available2019-05-31T11:04:17Z
dc.date.issued2019-07-01
dc.identifier.citationAli, N., Niada, S., Morris, M., Brini, A., Huen, D., Sumathi, V. and Latif, F. (2019) Comprehensive molecular characterization of adamantinoma and OFD-like adamantinoma bone tumors, The American Journal of Surgical Pathology, 43(7), pp. 965-974, 10.1097/PAS.0000000000001251en
dc.identifier.issn0147-5185en
dc.identifier.doi10.1097/pas.0000000000001251en
dc.identifier.urihttp://hdl.handle.net/2436/622386
dc.description.abstractAdamantinoma and osteofibrous dysplasia (OFD)-like adamantinoma are rare primary bone tumors that are predominantly confined to the tibia. These 2 entities show similarities in location, histology, and radiologic appearance; however, adamantinoma is malignant and therefore differentiating between these bone tumors is essential for optimal patient care. To elucidate their genomic and transcriptomic alteration profiles and expand their etiological mechanisms, whole exome sequencing (WES) and RNA sequencing (RNA-Seq) were conducted on adamantinoma and OFD-like adamantinoma tumors. Copy number variation analysis using WES data revealed distinct chromosomal alteration profiles for adamantinoma tumors compared with OFD-like adamantinomas, allowing molecular differentiation between the 2 tumor subtypes. Combining WES and copy number variation analyses, the chromatin remodelling-related gene KMT2D was recurrently altered in 3/8 adamantinoma tumors (38%), highlighting the potential involvement of deregulated chromatin structure and integrity in adamantinoma tumorigenesis. RNA-Seq analysis revealed a novel somatic gene fusion (EPHB4-MARCH10) in an adamantinoma, the gene fusion was fully characterized. Hierarchical clustering analysis of RNA-Seq data distinctly clustered adamantinoma tumors from OFD-like adamantinomas, allowing to molecularly distinguish between the 2 entities. David Gene Ontology analysis of differentially expressed genes identified distinct altered pathways in adamantinoma and OFD-like adamantinoma tumors, highlighting the different histopathologic characteristics of these bone tumor subtypes. Moreover, RNA-Seq expression profiling analysis identified elevated expression of DLK1 gene in adamantinomas, serving as a potential molecular biomarker. The present study revealed novel genetic and transcriptomic insights for adamantinoma and OFD-like adamantinoma tumors, allowing to differentiate genetically and transcriptomically between the 2 lesions and identifying a potential diagnostic marker for adamantinomas.en
dc.formatapplication/PDFen
dc.languageen
dc.language.isoenen
dc.publisherOvid Technologies (Wolters Kluwer Health)en
dc.relation.urlhttps://insights.ovid.com/crossref?an=00000478-900000000-97666en
dc.subjectwhole exome sequencingen
dc.subjectRNA sequencingen
dc.subjectgene fusionen
dc.subjectbone tumouren
dc.subjectCNVen
dc.titleComprehensive molecular characterization of adamantinoma and OFD-like adamantinoma bone tumorsen
dc.typeJournal articleen
dc.identifier.journalThe American Journal of Surgical Pathologyen
dc.date.updated2019-05-21T14:36:53Z
dc.date.accepted2019-03-04
rioxxterms.funderUniversity of Wolverhamptonen
rioxxterms.identifier.projectUOW310519MMen
rioxxterms.versionAMen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2020-07-01en
dc.source.volume43
dc.source.issue7
dc.source.beginpage1
dc.source.beginpage965
dc.source.endpage1
dc.source.endpage974
dc.description.versionPublished version
refterms.dateFCD2019-05-31T11:03:38Z
refterms.versionFCDAM
refterms.dateFOA2019-05-31T11:04:18Z


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