t(5;11)(q33;p13) CAPRIN1/PDGFRB

2009-03-01   Jean-Loup Huret  

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

Chronic myeloproliferative disease with eosinophilia

Epidemiology

Only one case to date, a 59-year-old male patient.

Genes Involved and Proteins

Gene name
PDGFRB (platelet-derived growth factor receptor, beta polypeptide)
Location
5q32
Protein description
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 (cell cycle associated protein 1)
Location
11p13
Protein description
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

Description

5 CAPRIN1 - 3 PDGFRB. In-frame fusion between exon 7 of CAPRIN1 and exon 11 of PDGFRB.

Oncogenesis

The coiled-coil domains from CAPRIN1 would favour dimerization, with subsequent constitutive activation of the PDGFRB tyrosine kinase domain.

Article Bibliography

Pubmed IDLast YearTitleAuthors
113318812001PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor.Bergsten E et al
172106332007Distinct 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 et al
172965642007Characterization 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 et al

Citation

Jean-Loup Huret

t(5;11)(q33;p13) CAPRIN1/PDGFRB

Atlas Genet Cytogenet Oncol Haematol. 2009-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1543/t(5;11)(q33;p13)