| Written | 2015-07 | Molly C. Schroeder, Shashirekha Shetty |
| The Center for Human Genetics Laboratory, University Hospitals, Cleveland, Ohio, USA Molly.Schroeder@alumni.bcm.edu; Robert J. Tomisch Pathology, Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA. shettys@ccf.org |
| Abstract |
| Abstract | The t(5;17)(q33;p13) rearrangement has been observed as sole cytogenetic abnormality in one case of chronic myelomonocytic leukemia, a soft-tissue aneurysmal bone cyst, and a case of myeloid and lymphoid neoplasms (MLNs) with eosinophilia. The t(5;17)(q33;p13) generates a fusion gene, located on the rearranged chromosome 5, comprised of the 5' portion of RABEP1 (encoding the coiled-coil domain) and the 3' portion of PDGFRB (encoding the intracellular kinase domain). Expression of the resulting fusion protein has been demonstrated to cause myeloproliferative disease in mice. |
| Identity |
| ICD-Topo | C400-C403,C408-C414,C418-C419 |
| Atlas_Id | 6977 |
| Phylum | Bones::Aneurysmal bone cyst |
 | |
| t(5;17)(q33;p13) in G-banded chromosomes. |
| Clinics and Pathology |
| Disease | Aneurysmal bone cyst (primary) |
| Note | t(5;17)(q33;p13) RABEP1/PDGFRB in hematological malignancies has also been described. |
| Epidemiology | One case of aneurysmal bone cyst with t(5;17)(q33;p13) to date: a white female patient who was 10 years old at diagnosis (Ellison et al., 2007). |
| Clinics | Patient developed limp and contracture after a fall down stairs. MRI revealed a cystic mass soft-tissue mass in posterior medial aspect of the left thigh (Ellison et al., 2007). |
| Cytology | Fibrous tissue and multinucleated giant cells observed on frozen section (Ellison et al., 2007). |
| Pathology | Mass of fibrous tissue with areas of bone rimmed with bony trabeculae (Ellison et al., 2007). |
| Treatment | Resection |
| Cytogenetics |
| Cytogenetics Morphological | Cytogenetic analysis has revealed t(5;17)(q33;p13) as a sole abnormality. |
| Cytogenetics Molecular | Metaphase FISH analysis with PDGFRB break apart probe reveals rearrangement of 5q33, interphase FISH with probe encompassing RABEP1 locus reveals rearrangement of 17p13. Reported only as a sole anomaly. |
| Probes | LPH031-A, CytoCell, Cambridge, UK. RP11-457I18, Blue Gnome, Cambridge, UK. |
| Genes involved and Proteins |
| Gene Name | PDGFRB (platelet-derived growth factor receptor, beta polypeptide) |
| Location | 5q32 |
| Note | chr5:150,113,839-150,155,859 (hg38) |
| Dna / Rna | Gene is 42 kb and contains 26 exons. Transcription occurs in telomere to centromere orientation. 5 transcripts are reported. |
 | |
| PDGFRB transcripts, from NCBI Gene report for Gene ID: 5159, updated 12-May-2015. | |
| Protein | PDGRFB encodes a tyrosine kinase receptor that is located on the plasma membrane and is activated by binding of members of the platelet-derived growth factor family of proteins. The product of the largest transcript is 1106 amino acids. Composed from NH2 to COOH of: Ig-like extracellular domains, a transmembrane domain, and a cytosolic tyrosine kinase domain. |
| Gene Name | RABEP1 (rabaptin, RAB GTPase binding effector protein 1) |
| Location | 17p13.2 |
| Note | chr17: 5,282,263-5,385,812 (hg38) |
| Dna / Rna | Gene is 103 kb and contains 20 exons. Transcription occurs in centromere to telomere orientation. 6 transcripts are reported. |
 | |
| RABEP1 transcripts, from NCBI Gene report for Gene ID: 9135, updated 4-May-2015. | |
| Protein | RABEP1 encodes a protein involved in endocytic membrane fusion and the trafficking of recycling endosomes. The product of the largest transcript is 826 amino acids and contains coiled-coil domains, a NH2-terminal RAB4 binding site, and a COOH-terminal RAB5 binding site. |
| Result of the chromosomal anomaly |
| Hybrid Gene | |
| Description | 5' RABEP1- 3' PDGFRB; no reciprocal transcript. |
| Fusion Protein | |
 | |
| Description | A schematic of the fusion transcript generated by the t(5;17)(q33;p13) rearrangement. Modified from Magnusson et al., 2001. |
| Description | 1318 amino acid fusion protein, including the first 739 aa of RABEP1 fused to the transmembrane and cytosolic tyrosine kinase domains of PDGFRB. |
| Oncogenesis | Expression of the fusion protein via infection with a MSCV-based retroviral plasmid was sufficient to transform Ba/F3 cells such that they grew independent of IL-3 (Magnusson et al., 2001). Expression of the fusion gene in murine bone marrow cells transplanted into lethally irradiated mice caused development of fatal myeloproliferative disorder (Magnusson et al., 2001). |
| Bibliography |
| Soft-Tissue Aneurysmal Bone Cyst: Report of a Case with t(5:17)(q33;p13). |
| Ellison DA, Sawyer JR, Parham DM, Nicholas R. |
| Pediatric and Developmental Pathology 2007; 10: 46-49. |
| PMID 17378626 |
| Rabaptin-5 is a novel fusion partner to platelet-derived growth factor beta receptor in chronic myelomonocytic leukemia. |
| Magnusson MK, Meade KE, Brown KE, Arthur DC, Krueger LA, Barrett AJ, Dunbar CE. |
| Blood. 2001 Oct 15;98(8):2518-25. |
| PMID 11588050 |
| Citation |
| This paper should be referenced as such : |
| Schroeder MC, Shetty S |
| Bone: Aneurysmal bone cyst with t(5;17)(q33;p13) RABEP1/PDGFR |
| Atlas Genet Cytogenet Oncol Haematol. in press |
| On line version : http://AtlasGeneticsOncology.org/Tumors/t0517q33p13BoneCystID6977.html |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(5;17)(q33;p13) RABEP1/PDGFRB | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Sep 18 17:21:38 CEST 2017 |
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