Controversies in orthopaedic oncology.

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Abstract

[Indexed for MEDLINE] Conflict of interest statement: A. Puri is a member of the editorial board of The Bone & Joint Journal. P. Ruggieri reports consulting fees from Exactech and Stryker, unrelated to this study. M. T. Houdek reports consulting fees from Link Orthopedics, unrelated to this study. E. Botello reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Zimmer Biomet, all of which are unrelated to this study. G. V. Morris reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Implantcast, all of which are unrelated to this study. 2. Genes Chromosomes Cancer. 2025 Sep;64(9):e70068. doi: 10.1002/gcc.70068. BCOR-Mutated Conventional and Dedifferentiated Chondrosarcoma: A Clinicopathologic Study. Montoya-Cerrillo DM(1), Evans MG(2), Elliott A(2), Anyosa RC(3), Torres JV(1), Montgomery EA(1), Hornicek FJ(4), Temple HT(4), Crawford B(4), Trent J(5), Jonczak EE(5), D'Amato G(5), Rosenberg AE(1). Author information: (1)Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA. (2)Caris Life Sciences, Irving, Texas, USA. (3)Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. (4)Division of Orthopedic Oncology, University of Miami Miller School of Medicine, Miami, Florida, USA. (5)Division of Medical Oncology, University of Miami Miller School of Medicine, Miami, Florida, USA. Conventional and dedifferentiated chondrosarcoma encompass a group of malignant neoplasms that produce cartilaginous matrix and arise within or on the surface of bone. Conventional chondrosarcomas are graded on a three-tiered scale, whereas dedifferentiated chondrosarcoma is typically not graded but is considered a high-grade sarcoma and represents the most aggressive subtype with a poor prognosis. IDH1 (isocitrate dehydrogenase-1) and IDH2 (isocitrate dehydrogenase-2) are the most commonly mutated genes in conventional and dedifferentiated chondrosarcoma, followed in frequency by COL2A1 and TP53. IDH1/2 driver mutations are also commonly found in enchondroma, considered a benign precursor lesion of chondrosarcoma, and other malignancies such as gliomas, cholangiocarcinoma, and acute myeloid leukemia. In acute myeloid leukemia, the presence of concurrent BCOR (BCL-6 corepressor) loss-of-function mutations has been linked to disease relapse and resistance to treatment with IDH inhibitors. After identifying an index case of conventional chondrosarcoma with unusually aggressive clinical evolution, we investigated the clinicopathological features of 12 cases of BCOR-mutated conventional and dedifferentiated chondrosarcomas against a control group of 15 BCOR-wildtype (WT) cases to determine whether BCOR-mutated tumors had patterns of biological progression different from tumors with intact BCOR. All identified BCOR alterations led to loss-of-function by either missense or nonsense mutations. The prevalence of BCOR mutations occurred in 5% of conventional and dedifferentiated chondrosarcoma, and these were associated with larger tumor size (p = 0.024), metastasis at the time of diagnosis (p ≤ 0.001) and higher T category (3-4 vs. 1-2) (p = 0.009). Although larger studies are necessary to clarify the full impact of BCOR mutations on patients with conventional and dedifferentiated chondrosarcoma, our data indicate that BCOR genetic aberrations are associated with adverse clinical features. © 2025 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC. DOI: 10.1002/gcc.70068 PMCID: PMC12432482