Adamantinoma 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.
*Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham
∥Department of Musculoskeletal Pathology, The Royal Orthopaedic Hospital. Robert Aitken Institute of Clinical Research, University of Birmingham, Edgbaston, Birmingham
‡Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK
†IRCCS Orthopedic Institute Galeazzi
§Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Conflicts of Interest and Source of Funding: Supported in part by the Kuwait Medical Genetics Center (KMGC), Ministry of Health, Kuwait; and the Italian Ministry of Health (Ricerca Corrente L2029 and L4097, IRCCS Istituto Ortopedico Galeazzi). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Correspondence: Farida Latif, PhD, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK (e-mail: firstname.lastname@example.org).