t(4;5)(q21;q33) PRKG2/PDGFRB
2009-11-01 Jean-Loup Huret Affiliation1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Clinics and Pathology
Disease
Atypical myeloproliferative disease (a-MPD) and systemic mast cell disease (SMCD)
Epidemiology
3 cases to date, a 45-year-old female patient with a-MPD with basophilia and eosinophilia (Walz et al., 2007), a 61-year-old male patient with systemic mast cell disease (SMCD) and an associated chronic basophilic leukemia (Lahortiga et al., 2008), and a 45-year-old male patient with a SMCD with eosinophilia (Gallagher et al., 2008).
Prognosis
This translocation seems to respond well to imatinib therapy: the chromosomal anomaly disappered with imatinib in the first patient; in the second case, the patient remained in clinical and cytogenetic remission 3 years after imatinib was initiated; the third patient was alive and well after about 4 years of therapy with imatinib.
Genes Involved and Proteins
Note
The patient with SMCD and an associated chronic basophilic leukemia was negative for KIT mutations (Lahortiga et al., 2008).
Gene name
PRKG2 (protein kinase, cGMP-dependent, type II)
Location
4q21.21
Protein description
762 amino acids; comprises a coiled-coil domain (leucine zipper, amino acids 23-85), cGMP binding sites (168-285 and 286-417) and a serine-threonine kinase domain (453-711); involved in signaling pathway. Belongs to the family of cyclic GMP-dependent protein kinase. PRKG2 phosphorylates CFTR. PRKG2 is an ion transport regulator (Vaandrager et al., 2005). PRKG2 regulates SOX9-mediated transcription of collagen 2 through phosphorylation (Chikuda et al., 2004). It was found that PRKG2 has an anti-proliferative effect via suppression of SOX9 expression, inhibition of Akt phosphorylation, and G1 arrest in glioma cell lines (Swartling et al., 2009).
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.
Result of the Chromosomal Anomaly
Description
5 PRKG2 - 3 PDGFRB. In-frame fusion between exon 2 of PRKG2, a 5 bp insert derived from intron 2 of PRKG2, and a truncated version (last 33 bp) of exon 12 of PDGFRB in one case (Lahortiga et al., 2008), and In-frame fusion between exon 5 of PRKG2, a 17 bp insert derived from PRKG2 intron 5, and a 41 bp truncated version exon 12 of PDGFRB in another case (Walz et al., 2007).
Oncogenesis
The coiled-coil domain from PRKG2 would favour dimerization, with subsequent constitutive activation of the PDGFRB tyrosine kinase domain.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 33663081 | 2021 | Myeloid tumors accompanying systemic mastocytosis, basophilia, and abnormal platelet-derived growth factor receptor β: A case report. | 13 |
| 27648315 | 2016 | A 26-Year-Old Female with Systemic Mastocytosis with Associated Myeloid Neoplasm with Eosinophilia and Abnormalities of PDGFRB, t(4;5)(q21;q33). | 11 |
| 18166785 | 2008 | Activity of imatinib in systemic mastocytosis with chronic basophilic leukemia and a PRKG2-PDGFRB fusion. | 0 |
| 38471404 | 2024 | Aggressive systemic mastocytosis with the co-occurrence of PRKG2::PDGFRB, KAT6A::NCOA2, and RXRA::NOTCH1 fusion transcripts and a heterozygous RUNX1 frameshift mutation. | 0 |
| 28412213 | 2017 | Acute mast cell leukemia associated with t(4;5)(q21;q33). | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11331881 | 2001 | PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. | Bergsten E et al |
| 15466490 | 2004 | Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes. | Chikuda H et al |
| 18262053 | 2008 | Fusion of PRKG2 and SPTBN1 to the platelet-derived growth factor receptor beta gene (PDGFRB) in imatinib-responsive atypical myeloproliferative disorders. | Gallagher G et al |
| 18166785 | 2008 | Activity of imatinib in systemic mastocytosis with chronic basophilic leukemia and a PRKG2-PDGFRB fusion. | Lahortiga I et al |
| 19543319 | 2009 | Cyclic GMP-dependent protein kinase II inhibits cell proliferation, Sox9 expression and Akt phosphorylation in human glioma cell lines. | Swartling FJ et al |
| 15970484 | 2005 | Molecular properties and biological functions of cGMP-dependent protein kinase II. | Vaandrager AB et al |
| 17296564 | 2007 | 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 et al |
Summary
Fusion gene
PRKG2/PDGFRB PRKG2 (4q21.21) PDGFRB (5q32) M|PRKG2/PDGFRB PRKG2 (4q21.21) PDGFRB (5q32) M t(4;5)(q21;q32)|PRKG2/PDGFRB PRKG2 (4q21.21) PDGFRB (5q32) TIC
Citation
Jean-Loup Huret
t(4;5)(q21;q33) PRKG2/PDGFRB
Atlas Genet Cytogenet Oncol Haematol. 2009-11-01
Online version: http://atlasgeneticsoncology.org/haematological/1510/t(4
