t(5;12)(q33;q24) GIT2/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

Epidemiology

Only one case to date, a 67-year-old male patient with a five years history of eosinophilia.

Prognosis

The patient was alive and well after 16 months of therapy with imatinib.

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
GIT2 (GIT ArfGAP 2)
Location
12q24.11
Protein description
Numerous isoforms; the longest is made of 759 amino acids; comprises an Arf-GAP domain (amino acids 1-124), zinc-fingers (11-34), ankyrin repeats (132-161, 166-195, 199-228, according to Swiss-Prot), a Spa2-homology domain, a coiled-coil domain (leucine zipper), and a paxillin-binding site (643-679). GIT1 and GIT2 belong to the family of ADP-ribosylation factor GTPase-activating proteins (ARF-GAP). GIT1 and GIT2 form homodimers and heterodimers which bind in oligomeric complex to the p21-activated kinase-interacting exchange factor proteins ARHGEF6 and ARHGEF7, to regulate the small GTP-binding proteins RAC1 and CDC42. Associates with paxillin, and with phospholipase C (PLCG). GIT1 and GIT2 also participate in receptor internalization by regulating membrane trafficking (Hoefen and Berk, 2006).

Result of the Chromosomal Anomaly

Description

5 GIT2 - 3 PDGFRB. In-frame fusion between exon 12 of GIT2, and exon 11 of PDGFRB.

Bibliography

Pubmed IDLast YearTitleAuthors
113318812001PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor.Bergsten E et al
165980762006The multifunctional GIT family of proteins.Hoefen RJ 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

Summary

Fusion gene

GIT2/PDGFRB GIT2 (12q24.11) PDGFRB (5q32) M t(5;12)(q32;q24)|GIT2/PDGFRB GIT2 (12q24.11) PDGFRB (5q32) TIC

Citation

Jean-Loup Huret

t(5;12)(q33;q24) GIT2/PDGFRB

Atlas Genet Cytogenet Oncol Haematol. 2009-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1544/t(5;12)(q33;q24)

External Links