| Clinics and Pathology |
| Disease | Chronic myeloproliferative disease with eosinophilia |
| 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. |
| Cytogenetics |
| Cytogenetics Morphological | The t(5;12) was the sole anomaly. |
| 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 | GIT2 |
| Location | 12q24 |
| Protein | 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. |
| External links |
| Other database | t(5;12)(q33;q24) | 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 |
| The multifunctional GIT family of proteins. |
| Hoefen RJ, Berk BC. |
| J Cell Sci. 2006 Apr 15;119(Pt 8):1469-75. (REVIEW) |
| PMID 16598076 |
| 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) |
| Written | 03-2009 | Jean-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;12)(q33;q24). Atlas Genet Cytogenet Oncol Haematol. March 2009 . URL : http://AtlasGeneticsOncology.org/Anomalies/t0512q33q24ID1544.html |
This paper is referenced by INIST as such : |
| http://documents.irevues.inist.fr/bitstream/2042/44692/1/03-2009-t0512q33q24ID1544.pdf [ Bibliographic record ] |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Mar 9 12:37:16 CET 2013 |
For comments and suggestions or contributions, please contact us