Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and Osteoclastogenesis
Giant cell tumour of bone (GCTB) is a rare and intriguing primary bone neoplasm. Worrisome clinical features are its local destructive behaviour, its high tendency to recur after surgical therapy and its ability to create so-called benign lung metastases (lung ‘plugs’). GCTB displays a complex and d...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/20/5119 |
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| author | Ramses G. Forsyth Tibor Krenács Nicholas Athanasou Pancras C. W. Hogendoorn |
| author_facet | Ramses G. Forsyth Tibor Krenács Nicholas Athanasou Pancras C. W. Hogendoorn |
| author_sort | Ramses G. Forsyth |
| collection | DOAJ |
| description | Giant cell tumour of bone (GCTB) is a rare and intriguing primary bone neoplasm. Worrisome clinical features are its local destructive behaviour, its high tendency to recur after surgical therapy and its ability to create so-called benign lung metastases (lung ‘plugs’). GCTB displays a complex and difficult-to-understand cell biological behaviour because of its heterogenous morphology. Recently, a driver mutation in histone H3.3 was found. This mutation is highly conserved in GCTB but can also be detected in glioblastoma. Denosumab was recently introduced as an extra option of medical treatment next to traditional surgical and in rare cases, radiotherapy. Despite these new insights, many ‘old’ questions about the key features of GCTB remain unanswered, such as the presence of telomeric associations (TAs), the reactivation of hTERT, and its slight genomic instability. This review summarises the recent relevant literature of histone H3.3 in relation to the GCTB-specific G34W mutation and pays specific attention to the G34W mutation in relation to the development of TAs, genomic instability, and the characteristic morphology of GCTB. As pieces of an etiogenetic puzzle, this review tries fitting all these molecular features and the unique H3.3 G34W mutation together in GCTB. |
| first_indexed | 2024-03-10T06:40:36Z |
| format | Article |
| id | doaj.art-930b6c789be544ab961867ca8e5c76b0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:40:36Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-930b6c789be544ab961867ca8e5c76b02023-11-22T17:40:35ZengMDPI AGCancers2072-66942021-10-011320511910.3390/cancers13205119Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and OsteoclastogenesisRamses G. Forsyth0Tibor Krenács1Nicholas Athanasou2Pancras C. W. Hogendoorn3Department of Pathology, University Hospital Brussels (UZB), Laarbeeklaan 101, 1090 Brussels, Belgium1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllöi ut 26, 1085 Budapest, HungaryDepartment of Histopathology, Nuffield Orthopaedic Centre, University of Oxford, NDORMS, Oxford OX3 7HE, UKDepartment of Pathology, University Hospital Brussels (UZB), Laarbeeklaan 101, 1090 Brussels, BelgiumGiant cell tumour of bone (GCTB) is a rare and intriguing primary bone neoplasm. Worrisome clinical features are its local destructive behaviour, its high tendency to recur after surgical therapy and its ability to create so-called benign lung metastases (lung ‘plugs’). GCTB displays a complex and difficult-to-understand cell biological behaviour because of its heterogenous morphology. Recently, a driver mutation in histone H3.3 was found. This mutation is highly conserved in GCTB but can also be detected in glioblastoma. Denosumab was recently introduced as an extra option of medical treatment next to traditional surgical and in rare cases, radiotherapy. Despite these new insights, many ‘old’ questions about the key features of GCTB remain unanswered, such as the presence of telomeric associations (TAs), the reactivation of hTERT, and its slight genomic instability. This review summarises the recent relevant literature of histone H3.3 in relation to the GCTB-specific G34W mutation and pays specific attention to the G34W mutation in relation to the development of TAs, genomic instability, and the characteristic morphology of GCTB. As pieces of an etiogenetic puzzle, this review tries fitting all these molecular features and the unique H3.3 G34W mutation together in GCTB.https://www.mdpi.com/2072-6694/13/20/5119giant cell tumour of boneosteoclastmononuclear spindle-shaped celltelomeric associationG34W |
| spellingShingle | Ramses G. Forsyth Tibor Krenács Nicholas Athanasou Pancras C. W. Hogendoorn Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and Osteoclastogenesis Cancers giant cell tumour of bone osteoclast mononuclear spindle-shaped cell telomeric association G34W |
| title | Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and Osteoclastogenesis |
| title_full | Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and Osteoclastogenesis |
| title_fullStr | Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and Osteoclastogenesis |
| title_full_unstemmed | Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and Osteoclastogenesis |
| title_short | Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and Osteoclastogenesis |
| title_sort | cell biology of giant cell tumour of bone crosstalk between m wt nucleosome h3 3 telomeres and osteoclastogenesis |
| topic | giant cell tumour of bone osteoclast mononuclear spindle-shaped cell telomeric association G34W |
| url | https://www.mdpi.com/2072-6694/13/20/5119 |
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