ArticleScientific reports2021
Profiling of three H3F3A-mutated and denosumab-treated giant cell tumors of bone points to diverging pathways during progression and malignant transformation.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 17 citations in OpenAlex.
- Incidence of malignant transformation in giant cell tumor of bone following denosumab therapy: a systematic review and meta-analysis.Journal of bone oncology · 2026Review
- Giant Cell Tumor of Bone: Biology, Pathophysiology, and Histopathology in the Era of H3F3A.Biomedicines · 2026Review
- Malignant Giant Cell Tumor of Bone: A Study of Clinical, Pathological, and Prognostic Profile from One Single Center.Bioengineering (Basel, Switzerland) · 2025Article
- Epigenetic roles of chromatin remodeling complexes in bone biology and the pathogenesis of bone‑related disease (Review).International journal of molecular medicine · 2025Review
- Establishment and characterization of NCC-GCTB10-C1: a novel cell line derived from a patient with recurrent giant cell tumor of bone.Human cell · 2024Article
- Current indications for denosumab in benign bone tumours.EFORT open reviews · 2023Review
- Denosumab for giant cell tumors of bone from 2010 to 2022: a bibliometric analysis.Clinical and experimental medicine · 2023Review
- Article
- Genetic characterization of a novel organoid from human malignant giant-cell tumor.Journal of bone oncology · 2023Article
- Potential alternative drug treatment for bone giant cell tumor.Frontiers in cell and developmental biology · 2023Article
- Premalignant Conditions of Bone.Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2022Article
- Clinicopathological and histological analysis of secondary malignant giant cell tumors of bone without radiotherapy.Oncology letters · 2022Article
- The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases.Pathology oncology research : POR · 2022Article
- State of the Art and New Concepts in Giant Cell Tumor of Bone: Imaging Features and Tumor Characteristics.Cancers · 2021Review
- Circular RNA-Related CeRNA Network and Prognostic Signature for Patients with Osteosarcoma.Cancer management and research · 2021Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Giant cell tumor of bone (GCTB) is a locally aggressive lesion of intermediate malignancy. Malignant transformation of GCTB is a rare event. In 2013, the humanized monoclonal antibody against receptor activator of nuclear factor-κb-Ligand (RANKL) denosumab was approved for treatment of advanced GCTB. Since then, several reports have questioned the role of denosumab during occasional malignant transformation of GCTB. We report on three patients with H3F3A-mutated GCTBs, treated with denosumab. The tissue samples were analysed by histomorphology, immunohistochemistry, and in two instances by next generation panel sequencing of samples before and after treatment. One patient had a mutation of ARID2 in the recurrence of the GCTB under treatment with denosumab. One patient developed a pleomorphic sarcoma and one an osteoblastic osteosarcoma during treatment. Sequencing revealed a persisting H3F3A mutation in the osteosarcoma while the pleomorphic sarcoma lost the H3F3A mutation; however, a FGFR1 mutation, both in the recurrence and in the pleomorphic sarcoma persisted. In addition, the pleomorphic sarcoma showed an AKT2 and a NRAS mutation. These data are inconclusive concerning the role denosumab plays in the event of malignant progression/transformation of GCTB and point to diverging pathways of tumor progression of GCTB associated with this treatment.
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