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t(5;11)(q33;p13)

Clinics and Pathology

Disease Chronic myeloproliferative disease with eosinophilia
Epidemiology Only one case to date, a 59-year-old male patient.

Cytogenetics

Cytogenetics Morphological The translocation was complex.

Genes involved and Proteins

Gene Name PDGFRB
Location 5q33
Protein Comprises an extracellular part with 5 Ig-like C2 type domains, a transmembrane domain, and an intracellular part with a tyrosine kinase domain (made of two tyrosine kinase subdomains) for transduction of the signal. Receptor tyrosine kinase; receptor for PDGFB and PDGFD (Bergsten et al., 2001); forms homodimers, or heterodimer with PDGFRA; upon dimerization, subsequent activation by autophosphorylation of the tyrosine kinase intracellular domains occurs.
Gene Name CAPRIN1
Location 11p13
Protein 709 amino acids. Comprises two coiled coil regions (amino acids 60-94 and 125-153) and a G3BP1-binding region (360-381), with, from 372 to 380 (FIQDSMLD), the conserved motif: F(M/I/L)Q(D/E)Sx(I/L)D (Solomon et al., 2007). Cytoplasmic phosphoprotein essential for normal cellular proliferation; CAPRIN1 occurs in messenger ribonucleoprotein particles that also contain RNA binding proteins; CAPRIN1/ G3BP1 complexes occur in RNA granules called cytoplasmic stress granules, which form in stressed cells. CAPRIN1 induces phosphorylation of eIF-2alpha. CAPRIN1 selectively binds mRNA for c-MYC and CCND2 (cyclin D2) (Solomon et al., 2007).

Result of the chromosomal anomaly

Hybrid gene
Description 5' CAPRIN1 - 3' PDGFRB. In-frame fusion between exon 7 of CAPRIN1 and exon 11 of PDGFRB.
  
Fusion Protein
Oncogenesis The coiled-coil domains from CAPRIN1 would favour dimerization, with subsequent constitutive activation of the PDGFRB tyrosine kinase domain.
  

External links

Other databaset(5;11)(q33;p13) Mitelman database (CGAP - NCBI)

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.

Bibliography

PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor.
Bergsten E, Uutela M, Li X, Pietras K, Ostman A, Heldin CH, Alitalo K, Eriksson U.
Nat Cell Biol. 2001 May;3(5):512-6.
PMID 11331881
 
Distinct structural features of caprin-1 mediate its interaction with G3BP-1 and its induction of phosphorylation of eukaryotic translation initiation factor 2alpha, entry to cytoplasmic stress granules, and selective interaction with a subset of mRNAs.
Solomon S, Xu Y, Wang B, David MD, Schubert P, Kennedy D, Schrader JW.
Mol Cell Biol. 2007 Mar;27(6):2324-42. Epub 2007 Jan 8.
PMID 17210633
 
Characterization of three new imatinib-responsive fusion genes in chronic myeloproliferative disorders generated by disruption of the platelet-derived growth factor receptor beta gene.
Walz C, Metzgeroth G, Haferlach C, Schmitt-Graeff A, Fabarius A, Hagen V, Prummer O, Rauh S, Hehlmann R, Hochhaus A, Cross NC, Reiter A.
Haematologica. 2007 Feb;92(2):163-9.
PMID 17296564
 

Contributor(s)

Written03-2009Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Citation

This paper should be referenced as such :
Huret JL . t(5;11)(q33;p13). Atlas Genet Cytogenet Oncol Haematol. March 2009 .
URL : http://AtlasGeneticsOncology.org/Anomalies/t0511q33p13ID1543.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/44691/1/03-2009-t0511q33p13ID1543.pdf   [ Bibliographic record ]

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