Bone: Aneurysmal bone cyst with t(5;17)(q33;p13) RABEP1/PDGFRB

2015-07-01   Molly C. Schroeder  , Shashirekha Shetty  

1.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

Summary

Atlas Image
t(5;17)(q33;p13) in G-banded chromosomes.

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.

Clinics and Pathology

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.

Probes

LPH031-A, CytoCell, Cambridge, UK. RP11-457I18, Blue Gnome, Cambridge, UK.

Additional anomalies

Reported only as a sole anomaly.

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 description

Gene is 42 kb and contains 26 exons. Transcription occurs in telomere to centromere orientation. 5 transcripts are reported.
Atlas Image
PDGFRB transcripts, from NCBI Gene report for Gene ID: 5159, updated 12-May-2015.

Protein description

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 description

Gene is 103 kb and contains 20 exons. Transcription occurs in centromere to telomere orientation. 6 transcripts are reported.
Atlas Image
RABEP1 transcripts, from NCBI Gene report for Gene ID: 9135, updated 4-May-2015.

Protein description

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

Description

5 RABEP1- 3 PDGFRB; no reciprocal transcript.
Atlas Image
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).

Article Bibliography

Pubmed IDLast YearTitleAuthors

Citation

Molly C. Schroeder ; Shashirekha Shetty

Bone: Aneurysmal bone cyst with t(5;17)(q33;p13) RABEP1/PDGFRB

Atlas Genet Cytogenet Oncol Haematol. 2015-07-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/6977/css/js/lib/bootstrap.min.js