| Clinics and Pathology |
| Etiology | The most widely accepted pathogenetic mechanism of aneurysmal bone cysts involves a local circulatory disturbance leading to markedly increased venous pressure and the development of a dilated and enlarged vascular bed within the affected bone area. However, the recent identification of recurrent chromosome abnormalities has challenged this historical perception. |
| Clinics | Aneurysmal bone cysts (ABC) are benign lesions that occur more frequently in the metaphyses of long bones, especially distal femur, the proximal tibia and vertebral posterior bodies. It can occur at any age but most patients are diagnosed in the first 2 decades of life. It can exist as primary bone lesion or as secondary lesions arising in association with other osseous conditions, namely giant cell tumor, chondroblastoma, chondromyxoid fibroma and fibrous dysplasia. Pain and swelling are the most common complaints. |
| Pathology | As the name implies, the lesion is histopathologically characterized by hemorrhagic cystic and cavernous spaces surrounded by fibrous septa composed of mildly to moderately mitotically active spindle cells intermixed with scattered osteoclast-like multinucleated giant cells. Approximately 95% of ABC have typical histology whereas the remaining 5% are "solid" variants in which the usual cavernous channels and spaces may not be identified. An extraosseous couterpart of ABC has been described, sometimes referred to as ABC of soft tissues, and is histologically identical to ABC but diagnosed much less frequently. |
| Treatment | ABC is most frequently treated by curettage, but local recurrences can still occur in a substantial number of cases. |
| Cytogenetics |
| Cytogenetics Morphological | Chromosome bands 16q22 and/or 17p13 are non randomly rearranged in ABC, regardless of tumor type (classic, solid) and or location (osseous and extraosseous). A recurrent t(16;17)(q22;p13) has been identified, but other chromosomal segments as translocation partner for each chromosome have been described: t(1;17)(p34;p13) THRAP3 -USP6, t(3;17)(q21;p13) ZNF9 -USP6, t(9;17)(q22;p13) OMD -USP6, t(17;17)(q12;p13) COL1A1 -USP6 Although additional cases should be studied, it appears that in combined giant cell tumor and secondary aneurysmal bone cyst, both lesions can retain their characteristic chromosomal aberrations. |
| Genes involved and Proteins |
| Gene Name | USP6 (Ubiquitin Specific Protease 6). Also known as TRE-2 or TRE17. |
| Location | 17p13 |
| Dna / Rna | 7878 bp (major transcript) |
| Protein | 786 amino acids; USP6 is a hominoid-specific gene that was initially cloned form an Ewing sarcoma cell line. It arose from an evolutionary chimeric gene fusion between the TBC1D3 (also known as PRC17) and USP32 (NY-REN-60) genes, which are both located on the long arm of chromosome 17. Sequence comparisons indicate that the first 14 exons of USP6 are derived from TBC1D3(PRC17) whereas exons 15 to 30 are derived from USP32(10). TBC1D3(PRC17) is located at chromosome band 17q12 and encodes a protein with a TBC/GAP domain involved in Rab/Ypt GTPase signaling. USP32 is located at chromosome band 17q23 and encodes a protein composed of two EF-hand calcium-binding motifs, a myristoylation site, and a UBP domain. USP6 protein retains the TBC domain of TBC1D3 (PRC17) and the UBP domain of USP32. Because USP6 is absent in non-hominoid primates and is primarily expressed in testicular tissue, it has been suggested that USP6 contributed to hominoid speciation. Until recently USP6 function was poorly know but recent data suggest that USP6 is a component of a novel effector pathway for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling. |
| Gene Name | CDH11 (Cadherin 11 or Osteoblast Cadherin or OB-Cadherin) |
| Location | 16q21-q22.1 |
| Dna / Rna | 3.6 and 3.8 kb mRNA (two major transcripts) |
| Protein | 693 and 796 amino acids; Membrane protein that mediate calcium-dependent cell-cell adhesion, member of the cadherin superfamily. CDH11 seems to be highly expressed during the development and differentiation of the osteoblastic lineage, indicating an important role in bone development. Two splice variants have been identified, one of which encodes an isoform with a shorter cytoplasmic domain. |
| Result of the chromosomal anomaly |
| Hybrid Gene | |
| Description | 5 ΠCDH11- 3 ΠUSP6 |
| Fusion Protein | |
| Description | Fusion of the promoter region of CDH11 (noncoding exons 1 and 2) to the entire coding region of USP6, which starts on exon 2. Therefore, there is only a fusion gene but not a fusion protein. This type of gene fusion is known as promoter swapping and has been described in other solid tumors, including pleomorphic adenoma and lipoblastoma. |
| Oncogenesis | The oncogenic mechanism of CDH11-USP6 is still unknown but very likely involves transcription upregulation of USP6 mediated by the highly active CDH11 promoter. |
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| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 01-2002 | Paola Dal Cin |
| Updated | 06-2004 | Paola Dal Cin |
| Citation |
| This paper should be referenced as such : |
| Dal Cin P . Bone: Aneurysmal bone cysts. Atlas Genet Cytogenet Oncol Haematol. January 2002 . URL : http://AtlasGeneticsOncology.org/Genes/AneurBoneCystID5133.html |
| Dal Cin P . Bone: Aneurysmal bone cysts. Atlas Genet Cytogenet Oncol Haematol. June 2004 . URL : http://AtlasGeneticsOncology.org/Genes/AneurBoneCystID5133.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Aug 11 21:22:02 2008 |
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