Osteoclastic giant cell-rich tumors
2022-12-07 Paola Dal Cin, PhD , Judith VMG Bovée Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2.Leiden University Medical Center, Leiden The Netherlands
Classification
Definition
Giant cell-rich tumors of bone are a group of rare bone tumors e.g. aneurysmal bone cyst, non-ossifying fibroma, and giant cell tumor of bone having in osteoclast-type multinucleated giant cells. However, they harbor different clinical and histological features , as well as molecular alterations e.g. in giant cell tumor of bone H3-3A, non-ossifying fibroma KRAS, FGFR, NF1and aneurysmal bone cyst USP6. 1,2
| Osteoclastic giant cell-rich tumors | Genetic marker(s) |
|---|---|
| Aneurysmal bone cyst (ABC) | Balanced chromosomal translocations involving USP6 gene at 17p13.1, with the t(16;17)(q22;p13) 3 been the most frequent translocation (~30% of the cases). This rearrangement is associated with CDH11::USPS fusion, driving USPS expression via promoter swapping. 4,5 A variety of partner genes have been reported, including COL1A1,THRAP3,CNBP,OMD, SEC31A, FAT1,SPARC , FOSL2, RUNX2, ASAP1, TNC, SAR1A, EIF1, STAT3 , PAFAH1B1, USP9X, CNBP , CTNNB1, ANGPTL2, and LUM. 6,7 |
| Many other entities are now sharing the same USPS rearrangements, so called USPS-associated neoplasms 6 | |
| Giant cell tumor of the bone (GCTB) | Exclusively alterations in the H3-3A gene (95%) with p.Gly34Trp (~ 92%) followed by p.Gly34Leu, and other rare one, in both conventional and malignant forms of giant cell tumor. 8,9 Diploid karyotype with with few structural changes, and with non-random telomeric associations. 10 |
| HMGA2::NCOR2 fusion transcripts recently found in six osteoclastic giant cell-rich bone tumors, negative for H3.3 G35W, with simple and complex cytogentic rearrangements of 12q14 region. 11 Interesting similar HMGA2::NCOR2 fusion was detected ingiant cell tumor of soft tissue 12 and xanthogranulomatous epithelial tumors. 13 | |
| Denosumab remains a highly effective treatment option for patients with advanced GCTB. 14 | |
| Non-ossifying fibroma | Hotspot mutations in KRAS, FGFR1 and NF115,16 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 33480599 | 2021 | The 2020 WHO Classification of Tumors of Bone: An Updated Review. | Choi JH et al |
| 2 | 34742488 | 2021 | Giant Cell-Rich Tumors of Bone. | Hartmann W et al |
| 3 | 10502326 | 1999 | Recurrent t(16;17)(q22;p13) in aneurysmal bone cysts. | Panoutsakopoulos G et al |
| 4 | 15026324 | 2004 | USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst. | Oliveira AM et al |
| 5 | 28752842 | 2017 | USP6 activation in nodular fasciitis by promoter-swapping gene fusions. | Patel NR et al |
| 6 | 32635781 | 2020 | USP6-Associated Neoplasms: A Rapidly Expanding Family of Lesions. | Hiemcke-Jiwa LS et al |
| 7 | 32859633 | 2020 | Fusion of the Lumican (LUM) Gene With the Ubiquitin Specific Peptidase 6 (USP6) Gene in an Aneurysmal Bone Cyst Carrying a t(12;17)(q21;p13) Chromosome Translocation. | Panagopoulos I et al |
| 8 | 24162739 | 2013 | Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. | Behjati S et al |
| 9 | 31728625 | 2020 | Mutation-driven epigenetic alterations as a defining hallmark of central cartilaginous tumours, giant cell tumour of bone and chondroblastoma. | Venneker S et al |
| 10 | 11106078 | 2000 | Cytogenetic-morphologic correlations in aneurysmal bone cyst, giant cell tumor of bone and combined lesions. A report from the CHAMP study group. | Sciot R et al |
| 11 | 35181586 | 2022 | Recurrent Fusion of the Genes for High-mobility Group AT-hook 2 (HMGA2) and Nuclear Receptor Co-repressor 2 (NCOR2) in Osteoclastic Giant Cell-rich Tumors of Bone. | Panagopoulos I et al |
| 12 | 33742141 | 2021 | Recurrent novel HMGA2-NCOR2 fusions characterize a subset of keratin-positive giant cell-rich soft tissue tumors. | Agaimy A et al |
| 13 | 35690644 | 2022 | Xanthogranulomatous epithelial tumors and keratin-positive giant cell-rich soft tissue tumors: two aspects of a single entity with frequent HMGA2-NCOR2 fusions. | Dehner CA et al |
| 14 | 32541321 | 2020 | Current concepts in the treatment of giant cell tumour of bone. | van der Heijden L et al |
| 15 | 30549028 | 2019 | Activating mutations in the MAP-kinase pathway define non-ossifying fibroma of bone. | Baumhoer D et al |
| 16 | 30809793 | 2019 | Non-ossifying fibroma: A RAS-MAPK driven benign bone neoplasm. | Bovée JV et al |
Citation
Paola Dal Cin, PhD ; Judith VMG Bovée
Osteoclastic giant cell-rich tumors
Atlas Genet Cytogenet Oncol Haematol. 2022-12-07
Online version: http://atlasgeneticsoncology.org/solid-tumor/208995/osteoclastic-giant-cell-rich-tumors
